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Metabolic support for diabetes management

Metabolic support for diabetes management

The National Institutes of Heart-healthy recipes NIH -sponsored multicentre Metabplic AHEAD Action for Health in Diabetes Heart-healthy recipes, investigated the Metablic of lifestyle intervention suppoft changes in Herbal wellness solutions, fitness Heart-healthy recipes cardiovascular Suppor risk factors and Calisthenics workouts in diabtees with type 2 uspport In adults Heart-healthy recipes type 2 diabetes and overweight or obesity, the effect of antihyperglycemic agents on body weight should be considered when selecting pharmacotherapy [Grade D, Consensus]. Dual agent failure — For patients who have deterioration of glycemic management on dual therapy, the options include:. Choice among devices is usually based on patient preferences for features such as time to results usually 5 to 30 secondssize of display panel large screens may benefit patients with poor eyesightvoice readout for those with visual impairmentand smartphone app connectivity 2 Monitoring references Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. ca: GPAC Handbook.

Metabolic support for diabetes management -

Increased blood sugar levels translate into greater sugars and acids that attack the teeth and lead to gum diseases. Gingivitis can also occur as a result of increased blood sugar levels along with an inappropriate oral hygiene. Periodontitis is an oral disease caused by untreated gingivitis and which destroys the soft tissue and bone that support the teeth.

This disease may cause the gums to pull away from the teeth which may eventually loosen and fall out. Diabetic people tend to experience more severe periodontitis because diabetes lowers the ability to resist infection [82] and also slows healing. At the same time, an oral infection such as periodontitis can make diabetes more difficult to control because it causes the blood sugar levels to rise.

To prevent further diabetic complications as well as serious oral problems, diabetic persons must keep their blood sugar levels under control and have a proper oral hygiene. A study in the Journal of Periodontology found that poorly controlled type 2 diabetic patients are more likely to develop periodontal disease than well-controlled diabetics are.

Diabetics who receive good dental care and have good insulin control typically have a better chance at avoiding gum disease to help prevent tooth loss. Dental care is therefore even more important for diabetic patients than for healthy individuals.

Maintaining the teeth and gum healthy is done by taking some preventing measures such as regular appointments at a dentist and a very good oral hygiene. Also, oral health problems can be avoided by closely monitoring the blood sugar levels. Patients who keep better under control their blood sugar levels and diabetes are less likely to develop oral health problems when compared to diabetic patients who control their disease moderately or poorly.

Poor oral hygiene is a great factor to take under consideration when it comes to oral problems and even more in people with diabetes. Diabetic people are advised to brush their teeth at least twice a day, and if possible, after all meals and snacks.

However, brushing in the morning and at night is mandatory as well as flossing and using an anti-bacterial mouthwash. Individuals with diabetes are recommended to use toothpaste that contains fluoride as this has proved to be the most efficient in fighting oral infections and tooth decay.

Flossing must be done at least once a day, as well because it is helpful in preventing oral problems by removing the plaque between the teeth, which is not removed when brushing.

Diabetic patients must get professional dental cleanings every six months. In cases when dental surgery is needed, it is necessary to take some special precautions such as adjusting diabetes medication or taking antibiotics to prevent infection.

Looking for early signs of gum disease redness, swelling, bleeding gums and informing the dentist about them is also helpful in preventing further complications. Quitting smoking is recommended to avoid serious diabetes complications and oral diseases. Diabetic persons are advised to make morning appointments to the dental care provider as during this time of the day the blood sugar levels tend to be better kept under control.

Not least, individuals with diabetes must make sure both their physician and dental care provider are informed and aware of their condition, medical history and periodontal status. Because many patients with diabetes have two or more comorbidities, they often require multiple medications.

The prevalence of medication nonadherence is high among patients with chronic conditions, such as diabetes, and nonadherence is associated with public health issues and higher health care costs. One reason for nonadherence is the cost of medications. Being able to detect cost-related nonadherence is important for health care professionals, because this can lead to strategies to assist patients with problems paying for their medications.

Some of these strategies are use of generic drugs or therapeutic alternatives, substituting a prescription drug with an over-the-counter medication, and pill-splitting. Interventions to improve adherence can achieve reductions in diabetes morbidity and mortality, as well as significant cost savings to the health care system.

As self-management of diabetes typically involves lifestyle modifications, adherence may pose a significant self-management burden on many individuals.

one's perception of diabetes, or one's appraisal of how helpful self-management is is likely to relate to one's emotions e. motivation to change , which in turn, affects one's self-efficacy one's confidence in their ability to engage in a behaviour to achieve a desired outcome.

As diabetes management is affected by an individual's emotional and cognitive state, there has been evidence suggesting the self-management of diabetes is negatively affected by diabetes-related distress and depression.

In the case of children and young people, especially if they are socially disadvantaged, research suggests that it is important that healthcare providers listen to and discuss their feelings and life situation to help them engage with diabetes services and self-management.

To this end, treatment programs such as the Cognitive Behavioural Therapy - Adherence and Depression program CBT-AD [87] have been developed to target the psychological mechanisms underpinning adherence.

By working on increasing motivation and challenging maladaptive illness perceptions, programs such as CBT-AD aim to enhance self-efficacy and improve diabetes-related distress and one's overall quality of life. While weight loss is clearly beneficial in improving glycemic control in patients with diabetes type 2, [97] maintaining significant weight loss can be a very difficult thing to do.

In diabetic people who have a body mass index of 35 or higher, and who have been unable to lose weight otherwise, bariatric surgery offers a viable option to help achieve that goal. In a Patient-Centered Outcomes Research Institute funded study was published which analyzed the effects of three common types of bariatric surgery on sustained weight loss and long-lasting glycemic control in patients with diabetes type 2.

Diabetes type 1 is caused by the destruction of enough beta cells to produce symptoms; these cells, which are found in the Islets of Langerhans in the pancreas , produce and secrete insulin , the single hormone responsible for allowing glucose to enter from the blood into cells in addition to the hormone amylin , another hormone required for glucose homeostasis.

Hence, the phrase "curing diabetes type 1" means "causing a maintenance or restoration of the endogenous ability of the body to produce insulin in response to the level of blood glucose" and cooperative operation with counterregulatory hormones.

This section deals only with approaches for curing the underlying condition of diabetes type 1, by enabling the body to endogenously, in vivo , produce insulin in response to the level of blood glucose.

A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet cells , which would secrete the amounts of insulin, amylin and glucagon needed in response to sensed glucose. When islet cells have been transplanted via the Edmonton protocol , insulin production and glycemic control was restored, but at the expense of continued immunosuppression drugs.

Encapsulation of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant.

Research is being done at several locations in which islet cells are developed from stem cells. Stem cell research has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.

Julio Voltarelli, Dr. Carlos Eduardo Couri, Dr Richard Burt, and colleagues and it was the first study to use stem cell therapy in human diabetes mellitus This was initially tested in mice and in there was the first publication of stem cell therapy to treat this form of diabetes.

In the trial, severe immunosuppression with high doses of cyclophosphamide and anti-thymocyte globulin is used with the aim of "turning off" the immunologic system", and then autologous hematopoietic stem cells are reinfused to regenerate a new one.

In summary it is a kind of "immunologic reset" that blocks the autoimmune attack against residual pancreatic insulin-producing cells. Until December , 12 patients remained continuously insulin-free for periods ranging from 14 to 52 months and 8 patients became transiently insulin-free for periods ranging from 6 to 47 months.

Of these last 8 patients, 2 became insulin-free again after the use of sitagliptin, a DPP-4 inhibitor approved only to treat type 2 diabetic patients and this is also the first study to document the use and complete insulin-independendce in humans with type 1 diabetes with this medication.

In parallel with insulin suspension, indirect measures of endogenous insulin secretion revealed that it significantly increased in the whole group of patients, regardless the need of daily exogenous insulin use. Technology for gene therapy is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes.

In November the FDA approved Teplizumab a monoclonal antibody drug which aims to delay type 1 diabetes by reprogramming the immune system to stop mistakenly attacking pancreatic cells.

Type 2 diabetes is usually first treated by increasing physical activity, and eliminating saturated fat and reducing sugar and carbohydrate intake with a goal of losing weight. These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg 10 to 15 lb , most especially when it is in abdominal fat deposits.

Diets that are very low in saturated fats have been claimed to reverse insulin resistance. Cognitive Behavioural Therapy is an effective intervention for improving adherence to medication, depression and glycaemic control, with enduring and clinically meaningful benefits for diabetes self-management and glycaemic control in adults with type 2 diabetes and comorbid depression.

Testosterone replacement therapy may improve glucose tolerance and insulin sensitivity in diabetic hypogonadal men. The mechanisms by which testosterone decreases insulin resistance is under study. Recently [ when? The precise causal mechanisms are being intensively researched; its results may not simply be attributable to weight loss, as the improvement in blood sugars seems to precede any change in body mass.

This approach may become a treatment for some people with type 2 diabetes, but has not yet been studied in prospective clinical trials. MODY is a rare genetic form of diabetes, often mistaken for Type 1 or Type 2. The medical management is variable and depends on each individual case.

Several immunosuppressive drugs targeting the chronic inflammation in type 2 diabetes have been tested. Contents move to sidebar hide. Article Talk. Read Edit View history. Tools Tools. What links here Related changes Upload file Special pages Permanent link Page information Cite this page Get shortened URL Download QR code Wikidata item.

Download as PDF Printable version. Management of diabetes. Main article: Blood glucose monitoring. Main article: Diet in diabetes. Main article: Anti-diabetic drug. Main article: Insulin therapy. See also: Fluorescent glucose biosensors. Revista Espanola de Cardiologia.

doi : PMID American Diabetes Association. Retrieved Korean Diabetes Association. ISSN PMC Glycemic Targets: Standards of Medical Care in Diabetes ". Diabetes Care. A guidance statement from the American College of Physicians". Annals of Internal Medicine.

Journal of the American Geriatrics Society. S2CID Clinical Diabetes. Diabetes in America. Bethesda: National Diabetes Data Group. Diabetic Medicine. January Nephrology, Dialysis, Transplantation. Journal of Endocrinological Investigation.

Clinical Ophthalmology. March Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes". June Cardiovascular Therapeutics.

July JAMA Internal Medicine. April Canadian Family Physician. Diabetes Research and Clinical Practice. Annales Universitatis Mariae Curie-Sklodowska.

Sectio D. Archived from the original PDF on 19 October Retrieved 6 October NIHR Evidence Plain English summary. International Journal of Human-Computer Studies. December Journal of General Internal Medicine.

A review of reviews". Journal of Behavioral Medicine. JMIR Diabetes. NIHR Evidence. National Institute for Health and Care Research. Skip to main content. We have doctors located throughout New York City. Recognition U. Our Team Our endocrinologists and cardiologists specialize in helping patients manage diabetes and reduce their risk of developing complications of the disease.

Nidhi Agrawal , MD. Sonal Chaudhry , MD. Aaron R. Chidakel , MD. Sandra T. Foo , MD. Ira J. Goldberg , MD. Lauren H. Golden , MD. Diabetes Specialist. Alina Gouller , MD. Akankasha Goyal , MD. Stephen B. In addition, GLP-1 receptor agonists have been shown to slow the rate of decline in eGFR and prevent worsening of albuminuria, albeit to a lesser degree than SGLT2 inhibitors.

GLP-1 receptor agonists should be titrated slowly, with monitoring for GI side effects, which could precipitate dehydration and acute kidney injury AKI. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.

We avoid use of SGLT2 inhibitors in patients with frequent genitourinary yeast infections or bacterial urinary tract infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol use disorder because of increased risk for each while using these agents.

SGLT2 inhibitors should be held for procedures, colonoscopy preparation, and with poor oral intake to prevent diabetic ketoacidosis.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'. In general, we tolerate higher glycemic targets, and, if medication is required, we prefer a short-acting, low-dose sulfonylurea eg, glipizide , repaglinide , linagliptin , or cautious use of a GLP-1 receptor agonist or insulin.

See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Treatment' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Use in chronic kidney disease' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Clinical use of meglitinides'.

Without established cardiovascular or kidney disease — For most patients without established ASCVD or kidney disease who have persistent hyperglycemia while taking metformin mg per day or a lower maximally tolerated dose , we suggest a GLP-1 receptor agonist or basal insulin based on the results of the GRADE trial, a comparative effectiveness study of commonly used classes of glucose lowering medications algorithm 2 [ 10,54 ].

In the GRADE trial, choice of a second glucose-lowering medication was evaluated in patients with type 2 diabetes A1C 6. Participants with hyperglycemia despite taking maximum tolerated doses of metformin were randomly assigned to treatment with U glargine, liraglutide , glimepiride , or sitagliptin.

Over a mean follow-up of five years, all four medications lowered A1C levels. The proportion of individuals with severe hypoglycemia was highest in the glimepiride group 2. Liraglutide had the highest frequency of gastrointestinal side effects.

The treatment groups did not differ in the rate of the prespecified secondary micro- or macrovascular outcomes, including moderately or severely increased albuminuria, reduced kidney function, peripheral neuropathy, major adverse cardiovascular events MACE , hospitalization for HF, cardiovascular mortality, or overall mortality [ 54,55 ].

However, there was a small reduction in the incidence of any CVD defined as first incidence of MACE, hospitalization for unstable angina or HF, or revascularization in any arterial bed with liraglutide 6. The GRADE trial was designed and implemented prior to the availability of SGLT2 inhibitors.

SGLT2 inhibitors have lower glycemic efficacy compared with basal insulin and GLP-1 receptor agonists [ 20 ]. The cardiovascular benefit of SGLT2 inhibitors has not been demonstrated in those at low cardiovascular risk. Shorter-term trial data also support selection of the dual-acting GLP-1 and GIP receptor agonist tirzepatide as a second glucose-lowering agent, particularly in individuals for whom substantial body weight loss is a treatment goal.

Trial data for tirzepatide are reviewed separately. The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost algorithm 2.

These benefits are offset by risks of hypoglycemia and modest weight gain. Sulfonylureas can be used safely and effectively with dose adjustment, even in people at risk of hypoglycemia, but this requires a bit more attention. We prefer a shorter-duration sulfonylurea or one with relatively lower risk for hypoglycemia eg, glipizide , glimepiride , since longer-acting glyburide is associated with a higher risk of hypoglycemia, especially in older or frail patients.

In addition, there are good data providing reassurance of the cardiovascular safety of these sulfonylureas. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'. The glycemic efficacy of sulfonylureas in combination with other oral agents is illustrated by the findings of a meta-analysis of trials in which sulfonylureas were added to oral agents predominantly metformin or thiazolidinediones [ 56 ].

Compared with placebo, the addition of sulfonylureas to oral diabetes treatment lowered A1C by 1. The clinical use, side effects, and concerns about the cardiovascular safety of sulfonylureas are reviewed separately. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus".

SGLT2 inhibitors are associated with modest weight loss. With both medication classes, weight loss effects are stronger when the medication is combined with sustained efforts at dietary modification.

In patients with diabetes mellitus and biopsy-proven NASH, pioglitazone has been shown to improve fibrosis as well as inflammation and steatosis. GLPbased therapies also appear to improve liver biopsy evidence of NASH.

These studies are reviewed in detail separately. See "Management of nonalcoholic fatty liver disease in adults", section on 'Patients with NASH and diabetes'. The potential benefits of these drugs must be balanced with their associated adverse effects.

In particular, pioglitazone is not typically a first-choice agent due to adverse effects, including increased risk of weight gain, fluid retention, HF, fractures, and the potential increased risk of bladder cancer.

It may play a role in the treatment of selected patients with severe insulin resistance, NASH or nonalcoholic fatty liver disease , at low risk of fracture. Adverse effects of pioglitazone may be minimized by using 15 to 30 mg rather than the 45 mg highest dose.

See "Management of nonalcoholic fatty liver disease in adults", section on 'Patients with NASH and diabetes' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Adverse effects'.

Trials comparing other combinations are reviewed separately in the individual topics. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Glycemic efficacy'.

Dual agent failure — For patients who have deterioration of glycemic management on dual therapy, the options include:. Although guidelines suggest combining SGLT2 inhibitors and GLP-1 receptor agonists [ 1 ], we do not usually add an SGLT2 inhibitor to GLP-1 receptor agonist therapy for hyperglycemia alone given the absence of data showing additive cardiovascular and kidney benefit and increased patient burden cost, polypharmacy, adverse effects.

The choice of additional therapy should be individualized, as discussed above for patients with monotherapy failure, based on efficacy, glycemic target, risk of hypoglycemia, the patient's underlying comorbidities, impact on weight, side effects, and cost.

See 'Monotherapy failure' above. In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally discontinued, while metformin is continued. In patients on a DPP-4 inhibitor who are starting a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, the DPP-4 inhibitor should be discontinued.

Insulin dose requirements can decrease precipitously with the addition of these medications, requiring patient education and close follow-up with insulin dose adjustment in the short term to reduce the risk of hypoglycemia. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'.

In a meta-analysis of randomized trials evaluating the addition of a third agent in patients inadequately managed with two agents predominantly metformin and a sulfonylurea or metformin and a thiazolidinedione , triple-agent combinations reduced A1C to a greater extent than two agents [ 58 ].

In trials lasting 52 to 54 weeks, the addition of thiazolidinediones, GLP-1 receptor agonists, or SGLT2 inhibitors to metformin and sulfonylurea reduced A1C to a similar extent, and tirzepatide imparted even greater A1C reduction.

However, these trials did not directly compare the third-line agents with each other. Moreover, only the GRADE study was of sufficient duration to determine long-term glycemic effects.

For patients who are not well managed on two oral agents, switching to insulin may be less expensive than adding a third oral or injectable agent, depending on which insulin and which third oral or injectable agent is selected.

Insulin initiation and intensification — If a decision has been made to add insulin to oral hypoglycemic therapy in patients with type 2 diabetes, a single daily dose of either insulin NPH or detemir given at bedtime or insulin glargine or degludec given in the morning or at bedtime is a reasonable initial regimen [ 1 ].

Metformin , GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors can be continued when insulin is added, whereas sulfonylureas and pioglitazone are usually discontinued due to reduced efficacy in comparison with other combinations and to adverse effects [ 59 ].

Patients should measure blood glucose at appropriate times, and usually once to twice per day, depending on the insulin used and timing of administration. For example, if bedtime NPH is used, it should be adjusted based on fasting glucose levels.

More frequent self-monitoring should be implemented during insulin dose adjustment and when changes in daily activities traveling, changes in diet or exercise pattern or acute illness makes insulin adjustments necessary. The dose of basal or long-acting insulin may be adjusted every three to four days until fasting glucose targets are achieved.

Once an insulin regimen is stable, less frequent glucose monitoring may suffice. See "Insulin therapy in type 2 diabetes mellitus", section on 'Titrating dose'. Related Pathway s : Diabetes: Initiation and titration of insulin therapy in non-pregnant adults with type 2 DM.

For patients who continue to have poor glycemic management on basal insulin after titration, diet and exercise patterns should be reviewed. Potential next steps include adding rapid-acting insulin before the largest meal and then two or three meals if needed , adding a GLP-1 receptor agonist, or changing to premixed insulin twice daily figure 5.

Several premixed combinations of basal and prandial insulin or basal insulin and a GLP-1 receptor agonist are available. See "Insulin therapy in type 2 diabetes mellitus", section on 'Designing an insulin regimen' and "General principles of insulin therapy in diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

Use of an intensive insulin regimen with multiple daily injections MDI; similar to that used in type 1 diabetes may be necessary in insulin-deficient type 2 diabetes. Patients with type 2 diabetes on MDI or with insulin deficiency may benefit from devices used more commonly in type 1 diabetes such as insulin pumps or continuous glucose monitors.

See "Continuous subcutaneous insulin infusion insulin pump " and "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'.

MDI results in higher serum insulin concentrations and better glycemic management than that achieved with either an oral drug or basal insulin therapy alone [ 7 ]. MDI in type 2 diabetes may require large doses of insulin to overcome insulin resistance and can be associated with substantial weight gain averaging 8.

Patients with type 2 diabetes with generalized obesity or with central overweight, often with nonalcoholic fatty liver disease, frequently require insulin doses in the range of 65 to units per day or much higher. Although the total daily dose of insulin may be high, the insulin dose per kilogram is less remarkable.

High daily insulin requirements may prompt consideration of use of concentrated insulins, such as U glargine or U regular insulin. Concentrated insulin formulations deliver more potent insulins in smaller volumes, which is less cumbersome for patients and facilitates improved insulin absorption.

See "General principles of insulin therapy in diabetes mellitus", section on 'U regular insulin' and "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs'.

While use of concentrated insulins is often effective for glycemic management, the worsening obesity associated with high-dose insulin can result in progressively increasing insulin requirements. This phenomenon may then lead to reconsideration of addition of an insulin-sparing agent eg, GLP-1 receptor agonist or thiazolidinedione or bariatric surgery.

See 'Bariatric metabolic surgery' below and "Medical nutrition therapy for type 2 diabetes mellitus". The vast majority of these CVD safety studies were placebo-controlled and enrolled all or a majority of patients with pre-existing CVD or at high cardiovascular risk, representing a minority of the type 2 diabetes population.

The long-term benefits and risks of using one agent over another in the absence of diagnosed CVD or high atherosclerotic CVD ASCVD risk are less clear. Thus, the results of these trials are most applicable to patients similar to the trial population and not to all patients with type 2 diabetes [ 2,60 ].

Cardiovascular benefit has been demonstrated for some of these medications when taken in combination with metformin , but benefit has not been definitively established in drug-naïve patients at low to moderate cardiovascular risk. See 'Without established cardiovascular or kidney disease' above.

The cardiovascular effects of each diabetes drug when data are available is reviewed in the individual topics. See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus".

They can reduce A1C values slightly 0. They act predominantly by lowering glucose concentrations after meals but may be poorly tolerated because of flatulence and other gastrointestinal GI side effects. However, if they are started at a low dose 25 mg before meals and slowly increased, they can be effective in people who follow high-carbohydrate diets.

See "Alpha-glucosidase inhibitors for treatment of diabetes mellitus". Pramlintide is only approved for use in patients also taking prandial insulin, and therefore, it is not generally used in patients with type 2 diabetes.

It also has frequent GI side effects. See "Amylin analogs for the treatment of diabetes mellitus". In , another inhaled insulin preparation was approved by the US Food and Drug Administration FDA. Inhaled insulin causes a very rapid rise in serum insulin concentration similar to that after subcutaneous rapid-acting insulins and faster than that after subcutaneous regular insulin.

It is designed to be used to manage postprandial glucose levels. Inhaled insulin may cause a transient cough with each inhalation, and it requires pulmonary monitoring. It is used infrequently in patients with type 2 diabetes.

See "Inhaled insulin therapy in diabetes mellitus". Colesevelam's mechanism of action to improve glycemia is uncertain [ 64 ]. One possibility is that bile acid sequestrants act in the GI tract to reduce glucose absorption.

In a meta-analysis of five short-term trials 16 to 26 weeks in patients with type 2 diabetes inadequately treated with oral agents or insulin, the addition of colesevelam compared with placebo modestly reduced A1C levels mean difference 0.

The meta-analysis was limited by the high or unclear risk of bias in the individual trials. Side effects can include constipation, nausea, and dyspepsia. In contrast to its effects on LDL cholesterol, colesevelam increases triglyceride concentrations by approximately 20 percent [ 66,67 ].

The clinical implications of this increase are unknown. See "Lipoprotein classification, metabolism, and role in atherosclerosis", section on 'Apolipoprotein C-III'. Given the modest glucose-lowering effectiveness, expense, and limited clinical experience, we typically do not recommend colesevelam to improve glycemic management in patients with type 2 diabetes.

See "Management of hyperprolactinemia", section on 'Overview of dopamine agonists'. A quick-release formulation of bromocriptine has been approved by the FDA for the treatment of type 2 diabetes mellitus [ 68 ].

In short-term clinical trials in patients with type 2 diabetes mellitus, bromocriptine up to 4. Common side effects include nausea, vomiting, dizziness, and headache [ 70 ]. The mechanism of action in reducing blood sugar is unknown.

Given its modest glucose-lowering effect, very frequent GI side effects, and the availability of more effective drugs, we do not recommend bromocriptine for the treatment of type 2 diabetes. BARIATRIC METABOLIC SURGERY — In patients with type 2 diabetes and obesity, bariatric and metabolic surgical procedures that result in sustained, major weight loss have been shown to lead to at least temporary remission of diabetes in a substantial fraction of patients.

Bariatric surgical procedures are targeted at weight loss in the setting of obesity; the term "metabolic surgery" is used when a major goal of surgery is to improve diabetes or other metabolic diseases eg, nonalcoholic fatty liver disease. Patient selection — Surgical treatment of obesity is an option to treat type 2 diabetes in appropriate surgical candidates with [ 71 ]:.

Surgical treatment has also been endorsed in patients with type 2 diabetes with BMI 30 to Given the increasing availability of potent GLPbased therapies and lack of comparative effectiveness data for bariatric surgery and these potent agents, we review these options with our patients and engage in shared decision-making.

See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Diabetes education' and "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Indications'.

Outcomes — Unblinded trials have compared bariatric surgery with medical therapy for the treatment of type 2 diabetes see "Outcomes of bariatric surgery", section on 'Diabetes mellitus'.

However, relapse of diabetes usually occurs over time, with 35 to 50 percent of patients who initially achieved diabetes remission after surgery experiencing a recurrence [ 72,75 ].

Nevertheless, bariatric surgery improves glycemia substantially and significantly more than medication therapy, and most patients have marked improvement in glycemic management for at least 5 to 15 years after surgery.

The effects of bariatric surgery on diabetes-related complications are reviewed in detail elsewhere. See "Outcomes of bariatric surgery", section on 'Diabetic complications'. Risks and concerns — Despite these impressive metabolic results, concerns remain about acute postoperative complications including the need for reoperations and rehospitalizations and rare, but potentially severe, adverse events; the long-term success rates in maintaining weight loss [ 71,80,81 ]; and the reproducibility of the results in patients with an extensive history of diabetes or with different surgical teams [ 82 ].

Some weight regain is typical within two to three years of bariatric procedures, and different procedures result in different levels of weight loss and corresponding reductions in glycemia.

Bariatric surgical procedures are reviewed in detail elsewhere. See "Bariatric procedures for the management of severe obesity: Descriptions" and "Bariatric surgery for management of obesity: Indications and preoperative preparation" and "Bariatric operations: Early fewer than 30 days morbidity and mortality".

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately.

See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Diabetes mellitus in children" and "Society guideline links: Diabetic kidney disease". These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest.

This decision is based on glycated hemoglobin A1C assay results calculator 1 typically performed every three to six months after initial therapy. After a successful initial response to lifestyle intervention and oral therapy, the majority of patients do not maintain target A1C levels during the subsequent three to five years.

See 'Indications for a second agent' above. Options include glucagon-like peptide 1 GLP-1 receptor agonists, a dual-acting GLP-1 and glucose-dependent insulinotropic polypeptide GIP receptor agonist tirzepatide , sodium-glucose co-transporter 2 SGLT2 inhibitors, short-acting sulfonylureas eg, glipizide , glimepiride , repaglinide if sulfonylurea not chosen as initial therapy , insulin, dipeptidyl peptidase 4 DPP-4 inhibitors, and pioglitazone figure 1 and table 2.

For patients with persistent hyperglycemia while taking a maximally tolerated dose of metformin, the choice of a second medication should be individualized based on efficacy, risk for hypoglycemia, the patient's comorbid conditions, impact on weight, side effects, and cost.

These agents have been shown to have the best glycemic efficacy algorithm 1. Gastrointestinal GI side effects, contraindications, and cost may limit their use. To select a medication, we use shared decision-making with a focus on beneficial and adverse effects within the context of the degree of hyperglycemia as well as a patient's comorbidities and preferences algorithm 2.

See 'Established cardiovascular or kidney disease' above. The majority of patients in the cardiovascular and renal outcomes trials had established cardiovascular disease CVD or diabetic kidney disease DKD with severely increased albuminuria, and therefore, these are the primary indications for one of these drugs.

Patients at high CVD risk but without a prior event might benefit, but the data are less supportive. Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria.

The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost. algorithm 2.

Sports nutrition myths is a chronic health problem that is manageent progressive Muscular endurance benefits difficult to treat. Obesity zupport also becoming suport prevalent in people with type 1 diabetes; one study reported a Almond snacks increase in the last 20 Metabolic support for diabetes management 2. In addition, intensive insulin therapy and some antihyperglycemic medications are associated with weight gain which, in turn, leads to obesity-related comorbid conditions 3,4. The relationship between increasing body fat accumulation and adverse health outcomes exists throughout the range of overweight and obesity in men and women of all age groups 5. Weight loss has been shown to improve glycemic control by increasing insulin sensitivity and glucose uptake and diminishing hepatic glucose output 6.

Metabolic support for diabetes management -

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Curr Med Res Opin ;— Andersen SE, Christensen M. Hypoglycaemia when adding sulphonylurea to metformin: A systematic review and networkmeta-analysis. Br J Clin Pharmacol ;— Simpson SH, Lee J, Choi S, et al. Mortality risk among sulfonylureas: A systematic review and network meta-analysis.

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Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: Efficacy and safety over 2 years. Liakos A, Karagiannis T, Athanasiadou E, et al. Efficacy and safety of empagliflozin for type 2 diabetes: A systematic reviewand meta-analysis.

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Multicenter Insulin Lispro Study Group. Anderson JH Jr, Brunelle RL, Koivisto VA, et al. Improved mealtime treatment of diabetes mellitus using an insulin analogue. Clin Ther ;— Yki-Jarvinen H, Dressler A.

Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes.

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Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Horvath K, Jeitler K, Berghold A, et al. Long-acting insulin analogues versus NPH insulin human isophane insulin for type 2 diabetes mellitus.

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Wysham C, Bhargava A, Chaykin L, et al. All BMI thresholds should be reconsidered depending on the ancestry of the patient. For example, for patients of Asian descent, the BMI values above should be reduced by 2.

Metabolic surgery should be performed in high-volume centers with multidisciplinary teams that understand and are experienced in the management of diabetes and GI surgery. Metabolic surgery is a potentially cost-effective treatment option in obese patients with T2D. The clinical community should work together with health care regulators to recognize metabolic surgery as an appropriate intervention for T2D in people with obesity and to introduce appropriate reimbursement policies.

The DSS-II organizing committee and the partner diabetes organizations tasked a multidisciplinary group of 48 international authorities to develop a set of evidence-based recommendations.

This DSS-II Expert Committee included scholars representing diabetology, endocrinology, internal medicine, cardiology, gastroenterology, primary care, nutrition, and surgery, including official representatives of partner diabetes organizations Table 2.

To ensure maximum scholarship, voting delegates were chosen entirely from academicians, with no representatives from industry. Criteria used for evidence searching were based on methods used in previous consensus development conferences and systematic reviews of evidence 44 , 45 , adapted to serve the DSS-II objectives.

We used a highly selective, diabetes-focused approach only level-1 evidence from RCTs to assess comparative effectiveness of surgery versus nonsurgical therapies for T2D and to compare the glycemic effects of different operations. A broader evidence base was used RCTs plus high-quality observational studies for matters such as durability of glycemic control, surgical safety, and cardiovascular disease CVD risk reduction.

MEDLINE from 1 January through 15 June was searched to generate the first draft of the consensus document. Studies considered to appraise the evidence included RCTs and observational studies case-control and case-series , as appropriate for specific questions vide infra. These criteria are adapted from the methods of recent systematic reviews of bariatric surgery A simple meta-analysis was performed to present an integrated picture of existing evidence.

For evidence regarding comparative effectiveness of different surgical procedures on T2D, data were obtained only from RCTs in which different procedures were used expressly to treat diabetes.

For evidence regarding the effect of GI surgery on CVD events and CVD risk reduction, data were obtained from RCTs when available, as well as from long-term case-control studies, and from the most recent relevant meta-analyses.

For evidence regarding the durability of postoperative glycemic control, surgical safety in general, and comparative safety profiles of different operations, data were obtained from RCTs when available, from longitudinal case-series and case-control studies, and from the most recent relevant meta-analyses.

Herein we use standard level of evidence LoE descriptors, defined as follows: IA, evidence from meta-analysis of RCTs; IB, evidence from at least one RCT; IIA, evidence from at least one controlled study without randomization; IIB, evidence from at least one other type of quasi-experimental study; III, evidence from nonexperimental descriptive studies e.

After review and appraisal of evidence, two independent moderators developed online Delphi-like questionnaires 47 , 48 to measure the degree of consensus for a set of statements and recommendations that were believed to summarize and reflect available evidence.

DSS-II delegates who did not agree with proposed statements were asked to state their reasons and propose amendments. Three rounds of questionnaires were administered to test various amendments to the original statements that could increase consensus levels from the group.

Draft conclusions generated through this iterative process were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes WCITD , London, U.

Proceedings were open to public comment by other experts in the field members of the Faculty of WCITD and by the entire audience through opinion polls, using real-time electronic voting. Approximately professionals and stakeholders from 50 nations on five continents contributed to those discussions.

Finally, on 30 September , voting DSS-II delegates met face-to-face to define a final consensus document. The document with conclusions reached by the experts underwent a final review by DSS voting delegates and was then submitted to the appropriate committees and executive boards of partner organizations for formal approval Table 1.

We used a supermajority rule to define consensus. This grading scale is meant to indicate statements that reflect unanimous or near-unanimous opinions grade U and grade A , strong agreement with little variance grade B , or a consensus statement that reflects an averaging of more and possibly extremely diverse opinions grade C.

We report here both the grade of consensus and the exact percentage of agreement for each statement. Beyond inducing weight loss—related metabolic improvements, some operations engage mechanisms that improve glucose homeostasis independent of weight loss 6 , such as changes in gut hormones, bile acid metabolism, microbiota, intestinal glucose metabolism, and nutrient sensing 5 , 6 , 26 — Our analysis of these trials shows a median HbA 1c reduction of 2.

In all of these trials, final HbA 1c in the surgical groups was near 6. However, the majority of these RCTs have only examined 1- to 2-year results, and only a handful of them have examined results for 3—5 years.

Weights represent inverse variance of ORs or mean differences [MDs] and provide an indirect measure of the relevance of each study within the meta-analysis, as a function of individual study size and variance. B : Forest plot of the trials depicted in Fig. Data are arranged in order of increasing follow-up time.

A random-effects model was used to calculate the pooled standardized MD. The plot shows 15 sample points because some RCTs reported results from two different surgical arms separately. Center lines show medians; box limits indicate the 25th and 75th percentiles, as determined by R software; whiskers extend 1.

Data points are plotted as open circles. B : Change from baseline HbA 1c in each of the 11 RCTs displayed in Fig. C : Dot plot comparing baseline with final HbA 1c levels following surgery in each of the 11 RCTs displayed in Fig. However, the median disease-free period among such individuals with Roux-en-Y gastric bypass RYGB is 8.

With or without diabetes relapse, the large majority of patients who undergo surgery maintain substantial improvement of glycemic control from baseline for at least 5 LoE IB 20 to 15 LoE IIA 52 , 55 — 59 years.

Baseline duration of diabetes e. Baseline visceral fat area may also help to predict postoperative outcomes, especially among Asian patients with T2D, who typically have more visceral fat compared with Caucasians with diabetes of the same BMI Improvements in other critical outcomes, such as micro- and macrovascular complications of diabetes, CVD, cancer, and death, have been observed only in nonrandomized studies LoE IIA 3 , 52 , 57 , 61 — Teenagers appear to experience similar degrees of weight loss, diabetes remission, and improvement of cardiometabolic risk factors for at least 3 years after surgery No randomized trials, however, have yet compared the effectiveness and safety of surgery to those of conventional treatment options in adolescents.

Although some models have suggested that bariatric surgery may even be cost-saving, direct measurements of health care costs from clinical studies have not demonstrated that surgery decreases overall health care expenditures.

A long-term assessment of health care costs in subjects enrolled in the Swedish Obese Subjects SOS study was performed according to diabetes status at baseline, providing a comparison of drug-related and total health care expenditure for patients who undergo bariatric surgery versus matched control participants over 15 years Although total health care costs for the surgery group were higher for patients with euglycemia or prediabetes, there was no difference between the surgery and conventional treatment groups for patients with diabetes at baseline.

There are, however, several limitations of economic studies in this field, warranting further research vide infra. This implies differences in technical complexity, mechanisms of action, clinical outcomes, and safety profiles.

Empirical data suggest that proficiency of the operating surgeon is an important factor determining mortality, complications, reoperations, and readmissions Morbidity has also dramatically declined with laparoscopic approaches.

There are, however, still complications of surgery that may require reoperations and rehospitalizations. A recent multicenter study showed early reoperation and readmission rates after laparoscopic operations of 2. Biliopancreatic diversion BPD , classic type or duodenal switch BPD-DS , is the most complex procedure, requires longer operative time, and is associated with the highest perioperative mortality and morbidity rates Compared with RYGB, BPD results in more surgical complications and greater incidence of GI side effects 81 , as well as nutritional deficiencies 20 LoE IB.

Hence, differences in baseline iron status may explain the large variability in reported rates of postoperative iron deficiency. Risk of bone fractures after surgery is unclear. One retrospective cohort study showed no increased fracture risk, whereas another reported a 1.

Postprandial hypoglycemia can also occur, especially with RYGB 83 , The exact prevalence of symptomatic hypoglycemia is unknown. Severe hypoglycemia resistant to conservative therapy, however, is rare There has recently been increased interest in device-based GI interventions designed to reproduce some of the benefits of metabolic surgery.

Small human studies have examined numerous approaches, including space-occupying endoluminal devices 90 , gastric electrical stimulation 91 , duodenal and gastroduodenal endoluminal barriers 92 , 93 , and duodenal mucosal resurfacing clinical trial reg. NCT, clinicaltrials. Preliminary short-term results show variable degrees of efficacy, depending on the device, in improving glycemic and metabolic control in patients with obesity and T2D.

Available RCTs do not allow an assessment of the relative role of surgery versus conventional therapies in many clinical scenarios, including the long-term effects of the most commonly performed current procedure VSG , or of the effectiveness of surgery in different stages of disease severity. Few RCTs have compared surgical procedures head-to-head, specifically to treat T2D.

The current LoE is not sufficient to determine the role of surgery as a first-line treatment in most clinical scenarios, especially in mildly obese or merely overweight patients.

There are no available long-term RCTs directly comparing surgery versus modern pharmacological therapies with diabetes complications or CVD events as primary end points, or with sufficient size, duration, and completeness of follow-up to conclusively determine the effects of surgery on these hard outcomes.

Such trials, which are clearly warranted, should ideally be randomized, with adequate power and follow-up to examine microvascular and CVD outcomes as primary end points. Although long-term safety and efficacy of metabolic surgery have been demonstrated in several studies 20 , 52 , 55 — 59 , investigations with follow-up beyond 5 years are limited.

This is particularly relevant for some procedures such as VSG because of their relatively recent introduction into clinical practice.

There is also limited evidence regarding the appropriate frequency of monitoring of nutritional status and the effectiveness of different types and dosage of nutritional and vitamin supplementations.

There is a paucity of studies investigating the role of multimodality therapy with integration of pharmaceutical and surgical treatment to optimize outcomes of diabetes management. In particular, little is known about the role of complementary postoperative lifestyle and pharmaceutical interventions to increase and maintain diabetes remission or enhance glycemic control and lower the risk of diabetes complications.

Although available data suggest that metabolic surgery may be as effective in adolescents as in adults 66 , there is presently no level-1 evidence to assess the effectiveness of surgery compared with conservative treatment in this population.

In particular, there are minimal long-term data regarding the safety of metabolic surgery and the potential negative impact of nutritional deficits on growth. Although preliminary clinical evidence for some device-based GI interventions is promising, appropriate RCTs with adequate end points, sample size, and follow-up are necessary for formal consideration of such approaches in the treatment algorithm for T2D.

Modeling studies are prone to risks of overestimating cost-savings because they make assumptions about the durability of clinical benefits from metabolic surgery. For instance, weight regain and diabetes relapse have not been properly accounted for in many economic analyses.

Variations in nonsurgical treatments of obesity and diabetes, plus costs across different types of payers private versus public and across countries, also are likely to determine different levels of return on investment.

On the other hand, most studies so far examined patients receiving bariatric surgery primarily for severe obesity and with a relatively low prevalence of diabetes; these studies might underestimate economic value of surgery because cost-effectiveness appears to be greater in obese patients with diabetes at baseline compared with those without diabetes Additional cost-effectiveness studies of specific metabolic surgery procedures in different clinical scenarios, and based on RCT data, would greatly facilitate the decision-making process of policymakers determining insurance coverage for surgical treatment of T2D.

Studies designed to further elucidate these mechanisms represent an important research priority. See Table 3. Although obesity and T2D are often associated with one another, T2D is a disease entity with significant heterogeneity that presents distinct challenges for clinical care.

Therefore, the traditional model of bariatric surgery practice, which is shaped around the goal to induce weight loss and treat severe obesity, is not consistent with the principles and standards of modern diabetes care. A few examples below provide an idea of the conceptual and practical ramifications of using a disease-specific model of care when surgery is used specifically to treat T2D.

Offering GI surgery with the primary intent to treat T2D, instead of just as a weight reduction therapy, can influence the demographic characteristics and baseline disease states of patients who elect to undergo surgery. Patients choosing bariatric surgery are typically young, predominantly female, with relatively low prevalence of T2D for their BMI 3 , 4 , Although not surprising, these differences can significantly influence the outcomes of surgery e.

These implications, rather than the BMI of the target population, represent the fundamental distinction between bariatric and metabolic surgery, necessitating the development of a new, disease-based model of practice. Traditional bariatric surgery is primarily conceived of as an intervention that reduces the risk of future disease i.

Such mis conception is reflected in the fact that most guidelines and criteria for coverage of bariatric surgery today make no recommendation for early intervention and often delay access to surgery.

However, T2D is a progressive disease associated with increased risk for CVD and microvascular complications. Furthermore, evidence shows that metabolic improvement following surgery in patients with T2D correlates with shorter diabetes duration at baseline, possibly reflecting more preserved β-cell function 19 , 52 , This suggests that unnecessarily delaying access to surgery might reduce health benefits and cost-effectiveness of surgery in patients with diabetes.

Moreover, existing criteria used for coverage of bariatric surgery are of low relevance for metabolic surgery. For example, because BMI is not a standard diagnostic parameter or a measure of severity of T2D, using BMI thresholds as stand-alone criteria for metabolic surgery does not allow health care providers to appropriately select candidates for such operations or to define criteria for prioritization of this type of approach.

T2D, however, describes a continuum of hyperglycemic states, is a heterogeneous disorder, and is associated with complex metabolic dysfunctions that increase CVD risk, as well as morbidity and mortality.

Thus, it is necessary to define meaningful definitions of goals and successful treatment when surgery is used with the primary intent to treat T2D. Because even temporary months to years normalization of glycemic control or major long-term improvement of glycemia without remission confers potential benefits for patients with T2D, remission of diabetes, although desirable, should not be regarded as the only goal of metabolic surgery or the only measure of success.

The success of metabolic surgery needs to be defined in the larger context of comprehensive diabetes care plans. Metabolic surgery should be considered a means to achieve the glycemic control necessary to reduce risk of microvascular complications and CVD. To date, no high-quality RCT data have directly demonstrated reductions in microvascular complications or CVD events, compared with standard therapy.

Although these definitions have helped to improve standardization of reporting outcomes, their applications in routine clinical practice and research are problematic.

The DSS delegates felt that remission as currently defined should not be considered to be the sole clinical benefit justifying metabolic surgery usage, especially since remission requires removal of all diabetes medications, and metformin is often used in individuals without diabetes.

Furthermore, complementary pharmaceutical therapies such as metformin should not be discontinued simply to meet the definition of remission, and metformin as well as ACE inhibitors and statins should be maintained as needed to sustain adequate glycemic control and prevent diabetes complications.

Patient selection for metabolic surgery should be based on balancing surgical and other long-term risks with potential long-term benefits to individual patients, as with any operation Fig.

This trade-off needs to take into account factors such as baseline CVD risk due to metabolic disease and hyperglycemia that do not adequately respond to nonsurgical treatments, as well as conditions that could contraindicate any elective operation, such as prior abdominal surgery, risk of anastomotic dehiscence, or risks of deep vein thrombosis and pulmonary embolism.

Algorithm for the treatment of T2D, as recommended by DSS-II voting delegates. The indications above are intended for patients who are appropriate candidates for elective surgery. meds, medications. In addition, preoperative indicators other than BMI should be established to make patient selection for metabolic surgery diabetes relevant.

There are no data showing that baseline BMI predicts metabolic surgery success. Instead, strong evidence indicates that preoperative BMI, at least within the obese range, does not predict the benefits of GI surgery with regard to diabetes prevention 51 , 57 , remission 11 , 20 , 52 , 53 , 56 , 98 , 99 , relapse after initial remission 20 , or the magnitude of its effects on CVD events 62 , , cancer 61 , or death LoE IIA 51 , 53 , 56 , 61 — 63 , Overall, the surgical value seems to be more related to improved glucose homeostasis than weight loss per se 11 , 12 , 51 , 54 , 55 , 61 — Although baseline BMI per se does not predict outcomes in metabolic surgery, available evidence, including all existing RCTs, is based on studies that have included BMI ranges among their primary criteria for eligibility.

Inevitably, and until additional studies identify more robust predictors of outcomes, BMI ranges remain necessary to select patients who might benefit from metabolic surgery, based on extant data. However, additional diabetes-specific parameters should help to identify clinical scenarios where surgical treatment of T2D should be prioritized.

Indications for surgical treatment of T2D should be evaluated by a multidisciplinary clinical team following a comprehensive preoperative assessment of diabetes and metabolic health.

Exact diagnosis of the type of diabetes, screening for diabetes complications, and measurement of residual insulin secretory reserve have special relevance for the practice of metabolic surgery. The choice of surgical procedure should be based on evaluation of the risk-to-benefit ratio in individual patients, weighing long-term nutritional hazards versus effectiveness on glycemic control and CVD risk.

It is too early to establish a gold standard operation for metabolic surgery because of the paucity of RCTs comparing surgical procedures head-to-head. The opposite gradient exists for comparative safety of these operations 10 — 25 , 72 , 76 — 79 , — Evidence from these studies can be summarized as follows:.

RYGB versus BPD: BPD promotes greater T2D remission but more metabolic complications compared with RYGB LoE IB. RYGB versus LAGB: RYGB achieves greater diabetes remission compared with LAGB LoE IA.

RYGB is associated with higher risk of early postoperative complications but lower risk of long-term reoperations LoE IIA. RYGB versus VSG: Compared with VSG, RYGB promotes higher diabetes remission rates LoE IA , better lipid control LoE IA , similar risk of reoperation LoE IA , better quality of life LoE IB , and higher incidence of postoperative complications LoE IA.

Because sudden improvement of prolonged hyperglycemia can acutely worsen microvascular disease, particularly intensive early postoperative monitoring is warranted in patients known to be afflicted Table 3. Develop and evaluate criteria for surgery that are more appropriate than BMI alone in people with T2D.

Investigate the long-term effect of surgery on microvascular disease and CVD in high-quality studies RCTs especially and prospective, well-matched case-control studies. Investigate the long-term effectiveness and safety of metabolic surgery in adolescents as compared with alternative treatment options.

Identify specific clinical scenarios in patients with diabetes that warrant escalation of treatment and earlier consideration of surgery. Define the optimal use of therapies that combine surgical, pharmacological, and postoperative lifestyle-based treatments.

Increase understanding of surgical mechanisms, so as to improve use of current treatment options and develop effective, new alternative therapies. Investigate cost-effectiveness of specific procedures and of the use of surgery in distinct clinical scenarios to inform policymakers about optimal strategies to prioritize surgical access.

Funding and Duality of Interest. These sponsors played no role in the selection of voting delegates, the Delphi process, the DSS-II and WCITD programs, or the writing of this article. None of the DSS-II codirectors, members of the organizing committee, or voting delegates received payment for their efforts.

No other potential conflicts of interest relevant to this article were reported. Author Contributions. and D. chaired the writing committee for this article and spearheaded its development. contributed to the preparation of this report. The 48 voting delegates listed in Table 2 participated in a 4-month-long Delphi-like process to craft the 32 consensus statements, culminating in the DSS-II conference in London, U.

Patients with type 2 diabetes with generalized obesity or with central overweight, often with nonalcoholic fatty liver disease, frequently require insulin doses in the range of 65 to units per day or much higher. Although the total daily dose of insulin may be high, the insulin dose per kilogram is less remarkable.

High daily insulin requirements may prompt consideration of use of concentrated insulins, such as U glargine or U regular insulin.

Concentrated insulin formulations deliver more potent insulins in smaller volumes, which is less cumbersome for patients and facilitates improved insulin absorption.

See "General principles of insulin therapy in diabetes mellitus", section on 'U regular insulin' and "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs'.

While use of concentrated insulins is often effective for glycemic management, the worsening obesity associated with high-dose insulin can result in progressively increasing insulin requirements.

This phenomenon may then lead to reconsideration of addition of an insulin-sparing agent eg, GLP-1 receptor agonist or thiazolidinedione or bariatric surgery.

See 'Bariatric metabolic surgery' below and "Medical nutrition therapy for type 2 diabetes mellitus". The vast majority of these CVD safety studies were placebo-controlled and enrolled all or a majority of patients with pre-existing CVD or at high cardiovascular risk, representing a minority of the type 2 diabetes population.

The long-term benefits and risks of using one agent over another in the absence of diagnosed CVD or high atherosclerotic CVD ASCVD risk are less clear. Thus, the results of these trials are most applicable to patients similar to the trial population and not to all patients with type 2 diabetes [ 2,60 ].

Cardiovascular benefit has been demonstrated for some of these medications when taken in combination with metformin , but benefit has not been definitively established in drug-naïve patients at low to moderate cardiovascular risk.

See 'Without established cardiovascular or kidney disease' above. The cardiovascular effects of each diabetes drug when data are available is reviewed in the individual topics.

See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus".

They can reduce A1C values slightly 0. They act predominantly by lowering glucose concentrations after meals but may be poorly tolerated because of flatulence and other gastrointestinal GI side effects.

However, if they are started at a low dose 25 mg before meals and slowly increased, they can be effective in people who follow high-carbohydrate diets.

See "Alpha-glucosidase inhibitors for treatment of diabetes mellitus". Pramlintide is only approved for use in patients also taking prandial insulin, and therefore, it is not generally used in patients with type 2 diabetes.

It also has frequent GI side effects. See "Amylin analogs for the treatment of diabetes mellitus". In , another inhaled insulin preparation was approved by the US Food and Drug Administration FDA. Inhaled insulin causes a very rapid rise in serum insulin concentration similar to that after subcutaneous rapid-acting insulins and faster than that after subcutaneous regular insulin.

It is designed to be used to manage postprandial glucose levels. Inhaled insulin may cause a transient cough with each inhalation, and it requires pulmonary monitoring.

It is used infrequently in patients with type 2 diabetes. See "Inhaled insulin therapy in diabetes mellitus". Colesevelam's mechanism of action to improve glycemia is uncertain [ 64 ].

One possibility is that bile acid sequestrants act in the GI tract to reduce glucose absorption. In a meta-analysis of five short-term trials 16 to 26 weeks in patients with type 2 diabetes inadequately treated with oral agents or insulin, the addition of colesevelam compared with placebo modestly reduced A1C levels mean difference 0.

The meta-analysis was limited by the high or unclear risk of bias in the individual trials. Side effects can include constipation, nausea, and dyspepsia. In contrast to its effects on LDL cholesterol, colesevelam increases triglyceride concentrations by approximately 20 percent [ 66,67 ].

The clinical implications of this increase are unknown. See "Lipoprotein classification, metabolism, and role in atherosclerosis", section on 'Apolipoprotein C-III'. Given the modest glucose-lowering effectiveness, expense, and limited clinical experience, we typically do not recommend colesevelam to improve glycemic management in patients with type 2 diabetes.

See "Management of hyperprolactinemia", section on 'Overview of dopamine agonists'. A quick-release formulation of bromocriptine has been approved by the FDA for the treatment of type 2 diabetes mellitus [ 68 ]. In short-term clinical trials in patients with type 2 diabetes mellitus, bromocriptine up to 4.

Common side effects include nausea, vomiting, dizziness, and headache [ 70 ]. The mechanism of action in reducing blood sugar is unknown. Given its modest glucose-lowering effect, very frequent GI side effects, and the availability of more effective drugs, we do not recommend bromocriptine for the treatment of type 2 diabetes.

BARIATRIC METABOLIC SURGERY — In patients with type 2 diabetes and obesity, bariatric and metabolic surgical procedures that result in sustained, major weight loss have been shown to lead to at least temporary remission of diabetes in a substantial fraction of patients.

Bariatric surgical procedures are targeted at weight loss in the setting of obesity; the term "metabolic surgery" is used when a major goal of surgery is to improve diabetes or other metabolic diseases eg, nonalcoholic fatty liver disease.

Patient selection — Surgical treatment of obesity is an option to treat type 2 diabetes in appropriate surgical candidates with [ 71 ]:. Surgical treatment has also been endorsed in patients with type 2 diabetes with BMI 30 to Given the increasing availability of potent GLPbased therapies and lack of comparative effectiveness data for bariatric surgery and these potent agents, we review these options with our patients and engage in shared decision-making.

See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Diabetes education' and "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Indications'.

Outcomes — Unblinded trials have compared bariatric surgery with medical therapy for the treatment of type 2 diabetes see "Outcomes of bariatric surgery", section on 'Diabetes mellitus'.

However, relapse of diabetes usually occurs over time, with 35 to 50 percent of patients who initially achieved diabetes remission after surgery experiencing a recurrence [ 72,75 ]. Nevertheless, bariatric surgery improves glycemia substantially and significantly more than medication therapy, and most patients have marked improvement in glycemic management for at least 5 to 15 years after surgery.

The effects of bariatric surgery on diabetes-related complications are reviewed in detail elsewhere. See "Outcomes of bariatric surgery", section on 'Diabetic complications'. Risks and concerns — Despite these impressive metabolic results, concerns remain about acute postoperative complications including the need for reoperations and rehospitalizations and rare, but potentially severe, adverse events; the long-term success rates in maintaining weight loss [ 71,80,81 ]; and the reproducibility of the results in patients with an extensive history of diabetes or with different surgical teams [ 82 ].

Some weight regain is typical within two to three years of bariatric procedures, and different procedures result in different levels of weight loss and corresponding reductions in glycemia.

Bariatric surgical procedures are reviewed in detail elsewhere. See "Bariatric procedures for the management of severe obesity: Descriptions" and "Bariatric surgery for management of obesity: Indications and preoperative preparation" and "Bariatric operations: Early fewer than 30 days morbidity and mortality".

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately.

See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Diabetes mellitus in children" and "Society guideline links: Diabetic kidney disease". These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest.

This decision is based on glycated hemoglobin A1C assay results calculator 1 typically performed every three to six months after initial therapy. After a successful initial response to lifestyle intervention and oral therapy, the majority of patients do not maintain target A1C levels during the subsequent three to five years.

See 'Indications for a second agent' above. Options include glucagon-like peptide 1 GLP-1 receptor agonists, a dual-acting GLP-1 and glucose-dependent insulinotropic polypeptide GIP receptor agonist tirzepatide , sodium-glucose co-transporter 2 SGLT2 inhibitors, short-acting sulfonylureas eg, glipizide , glimepiride , repaglinide if sulfonylurea not chosen as initial therapy , insulin, dipeptidyl peptidase 4 DPP-4 inhibitors, and pioglitazone figure 1 and table 2.

For patients with persistent hyperglycemia while taking a maximally tolerated dose of metformin, the choice of a second medication should be individualized based on efficacy, risk for hypoglycemia, the patient's comorbid conditions, impact on weight, side effects, and cost.

These agents have been shown to have the best glycemic efficacy algorithm 1. Gastrointestinal GI side effects, contraindications, and cost may limit their use. To select a medication, we use shared decision-making with a focus on beneficial and adverse effects within the context of the degree of hyperglycemia as well as a patient's comorbidities and preferences algorithm 2.

See 'Established cardiovascular or kidney disease' above. The majority of patients in the cardiovascular and renal outcomes trials had established cardiovascular disease CVD or diabetic kidney disease DKD with severely increased albuminuria, and therefore, these are the primary indications for one of these drugs.

Patients at high CVD risk but without a prior event might benefit, but the data are less supportive. Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria.

The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost. algorithm 2.

See 'Dual agent failure' above. For most patients who do not achieve target A1C with initial dual therapy, we suggest starting insulin or a GLP-1 receptor agonist Grade 2B if neither already chosen as a second agent. In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally tapered and discontinued, while metformin is continued.

In patients on DPP-4 inhibitors who are starting a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, the DPP-4 inhibitor is discontinued, while metformin is continued. See 'Dual agent failure' above and 'Insulin initiation and intensification' above.

Related Pathway s : Diabetes: Initial therapy for non-pregnant adults with type 2 DM. An alternative is two oral agents and a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, particularly for patients in whom weight loss or avoidance of hypoglycemia is a primary consideration.

These GLPbased therapies should not be combined with DPP-4 inhibitors. Another option for patients close to glycemic goals is three oral agents eg, metformin , sulfonylurea plus: DPP-4 inhibitor, SGLT2 inhibitor, or pioglitazone. Although guidelines suggest combining SGLT2 inhibitors and GLP-1 receptor agonists, we do not usually add an SGLT2 inhibitor to GLP-1 receptor agonist therapy for management of hyperglycemia alone, given the absence of data showing additive cardiovascular and kidney benefit and increased patient burden cost, polypharmacy, adverse effects.

Bariatric surgery may also be an option in patients with lower BMI 30 to Patients seeking bariatric surgery should be counseled to develop coping skills, eliminate maladaptive behavior, and understand the risks and benefits of the surgery.

See 'Bariatric metabolic surgery' above and "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Preoperative counseling'. Why UpToDate? Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you.

Select the option that best describes you. View Topic. Font Size Small Normal Large. Management of persistent hyperglycemia in type 2 diabetes mellitus. Formulary drug information for this topic.

No drug references linked in this topic. Find in topic Formulary Print Share. View in. Language Chinese English. Author: Deborah J Wexler, MD, MSc Section Editor: David M Nathan, MD Deputy Editor: Katya Rubinow, MD Contributor Disclosures.

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan This topic last updated: Jan 11, Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes Diabetes Care ; S Davies MJ, Aroda VR, Collins BS, et al.

Management of hyperglycaemia in type 2 diabetes, A consensus report by the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD. Diabetologia ; Kirkman MS, Briscoe VJ, Clark N, et al.

Diabetes in older adults. Diabetes Care ; Wei N, Zheng H, Nathan DM. Empirically establishing blood glucose targets to achieve HbA1c goals. American Diabetes Association Professional Practice Committee. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS UK Prospective Diabetes Study UKPDS Group.

Lancet ; United Kingdom Prospective Diabetes Study UKPDS. BMJ ; prospective diabetes study Overview of 6 years' therapy of type II diabetes: a progressive disease. Prospective Diabetes Study Group. Diabetes ; Turner RC, Cull CA, Frighi V, Holman RR.

Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies UKPDS JAMA ; GRADE Study Research Group, Nathan DM, Lachin JM, et al. Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes. N Engl J Med ; Bressler P, DeFronzo RA.

Drugs and diabetes. Diabetes Reviews ; Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Shah BR, Hux JE, Laupacis A, et al. Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians?

Ziemer DC, Doyle JP, Barnes CS, et al. An intervention to overcome clinical inertia and improve diabetes mellitus control in a primary care setting: Improving Primary Care of African Americans with Diabetes IPCAAD 8. Arch Intern Med ; Grant RW, Buse JB, Meigs JB, University HealthSystem Consortium UHC Diabetes Benchmarking Project Team.

Quality of diabetes care in U. academic medical centers: low rates of medical regimen change. Fanning EL, Selwyn BJ, Larme AC, DeFronzo RA. Improving efficacy of diabetes management using treatment algorithms in a mainly Hispanic population.

Grant RW, Cagliero E, Sullivan CM, et al. A controlled trial of population management: diabetes mellitus: putting evidence into practice DM-PEP. Das SR, Everett BM, Birtcher KK, et al.

Diabetes mellitus is a foor in which the body does not produce diabbetes or respond normally to Metabolic support for diabetes managementflr blood sugar glucose levels to be abnormally high. Metabolic support for diabetes management of Almond snacks may Fat metabolism and weight management increased urination and Metabolkc, and people may Metabokic weight even if they are not trying to. Diabetes can damage blood vessels and increase the risk of heart attack, stroke, chronic kidney disease, and vision loss. People with diabetes need to follow a healthy diet that is low in refined carbohydrates including sugarsaturated fat, and processed foods. They also need to exercise, maintain a healthy weight, and usually take medications to lower blood sugar levels and promote weight loss if their weight is above a healthy level. Metabolic support for diabetes management People diaetes type 2 diabetes form a heterogeneous group. Consequently, treatment regimens dibetes therapeutic targets should be individualized. The Antioxidant rich breakfast recipes Almond snacks type 2 diabetes involves Almond snacks multi-pronged approach diaebtes aims to treat and prevent symptoms of hyperglycemia, such as dehydration, fatigue, polyuria, infections and hyperosmolar states; and to reduce the risks of cardiovascular CV and microvascular complications 1. This includes healthy behaviour interventions see Reducing the Risk of Diabetes chapter, p. S20; Cardiovascular Protection in People with Diabetes chapter, p. S and antihyperglycemic medications.

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