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Concept: Sulfonylurea

225

 To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones).

Concepts: Diabetes mellitus type 2, Diabetes mellitus, Insulin resistance, Anti-diabetic drug, Sulfonylurea, Pioglitazone, Thiazolidinedione, Rosiglitazone

221

 To assess diagnostic accuracy of screening tests for pre-diabetes and efficacy of interventions (lifestyle or metformin) in preventing onset of type 2 diabetes in people with pre-diabetes.

Concepts: Insulin, Diabetes mellitus type 2, Evaluation, Obesity, Diabetes, Insulin resistance, Sulfonylurea, Prevention

194

Since the first ADA working group report on the recommendations for management of diabetes during Ramadan in 2005 and our update in 2010, we received many inquiries asking for regular updates on information regarding education, nutritional habits and new oral and injectable agents that may be useful for the management of patients with diabetes during Ramadan. Patients can be stratified into their risk of hypoglycemia and/or complications prior to the start of the fasting period of Ramadan. Those at high risk of hypoglycemia and with multiple diabetic complications should be advised against prolonged fasting. Even in the lower hypoglycemia risk group, adverse effects may still occur. In order to minimize adverse side effects during fasting in patients with diabetes and improve or maintain glucose control, education and discussion of glucose monitoring and treatment regimens should occur several weeks prior to Ramadan. Agents such as metformin, thiazolidinediones and dipeptidyl peptidase-4 inhibitors appear to be safe and do not need dose adjustment. Most sulfonylureas may not be used safely during Ramadan except with extreme caution; besides, older agents, such as chlorpropamide or glyburide, should not be used. Reduction of the dosage of sulfonylurea is needed depending on the degree of control prior to fasting. Misconceptions and local habits should be addressed and dealt with in any educational intervention and therapeutic planning with patients with diabetes. In this regard, efforts are still needed for controlled prospective studies in the field of efficacy and safety of the different interventions during the Ramadan Fast.

Concepts: Therapeutic effect, Nutrition, Diabetes mellitus, Hypoglycemia, Sulfonylurea, Metformin, Adverse drug reaction, Fasting

184

Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

Concepts: Insulin, Diabetes mellitus type 2, Diabetes mellitus, Stem cell, Obesity, Embryonic stem cell, Sulfonylurea, Metformin

168

167

OBJECTIVES: Older patients are particularly vulnerable to hypoglycaemia. The aim of this study was to evaluate the response to initiation of once-daily insulin detemir in patients aged ≥75 years with type 2 diabetes mellitus (T2DM) treated with one or more oral antidiabetic drugs (OADs). METHODS: A sub-analysis was conducted using data from SOLVE (Study of Once daily LeVEmir), a 24-week observational study involving 3,219 investigators and 2,817 project sites from ten countries. Routine clinical practice was followed; there were no study-prescribed procedures. The total cohort comprised 17,374 participants, of whom 2,398 (14 %) were aged ≥75 years. The physicians collected information from patient recall, the patients' medical records and their self-monitored blood glucose diaries (if kept). RESULTS: Pre-insulin glycated haemoglobin (HbA(1c)) was similar between participants aged ≥75 years and those aged <75 years (HbA(1c) 8.8 ± 1.5 % vs. 8.9 ± 1.6 % [mean ± SD], respectively). After 24 weeks of treatment, similar reductions in HbA(1c) were observed in the two subgroups: 7.6 ± 1.1 % and 7.5 ± 1.2 % in participants aged ≥75 years and those aged <75 years, respectively. The incidence of severe hypoglycaemia (episodes per patient-year) decreased during the study in both age groups (from 0.057 to 0.007 in patients aged ≥75 years; from 0.042 to 0.005 in patients aged <75 years), while minor hypoglycaemia increased from 1.1 to 2.0 and from 1.7 to 1.8 episodes per patient-year in the older and younger age groups, respectively. Average weight reduction was similar in both groups: -0.5 kg (≥75 years) and -0.6 kg (<75 years). CONCLUSION: In both the older and younger age groups, the addition of once-daily insulin detemir to existing OAD regimens was effective and safe. In older patients, an improvement in HbA(1c) of 1.2 % was not associated with an increased risk of severe hypoglycaemia or weight gain.

Concepts: Insulin, Diabetes mellitus type 2, Diabetes mellitus, Obesity, Diabetes, Hypoglycemia, Anti-diabetic drug, Sulfonylurea

152

Evidence suggests that clinical outcomes for people with type 2 diabetes mellitus can be improved through multifactorial treatment. The key challenges in the successful treatment of type 2 diabetes include maintaining tight glycemic control, minimizing the risk of hypoglycemia, controlling cardiovascular risk factors, and reducing or controlling weight. The aim of the present analysis was to evaluate the cost per patient achieving a composite clinical end point (glycosylated hemoglobin <7%, with no weight gain and no hypoglycemic events) in patients with type 2 diabetes in Quebec, Quebec, Canada, receiving liraglutide 1.2 mg, liraglutide 1.8 mg, thiazolidinedione, sulfonylurea, insulin glargine, sitagliptin, or exenatide.

Concepts: Insulin, Diabetes mellitus type 2, Diabetes mellitus, Obesity, Diabetes, Insulin resistance, Hypoglycemia, Sulfonylurea

145

Sodium-glucose linked transporter 2 inhibition recently emerged as a promising therapy for reducing the risk of heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). However, there is a lack of data endorsing its role in symptomatic HF patients. We sought to evaluate the short-term effects of empagliflozin on maximal exercise capacity in these patients.

Concepts: Hypertension, Insulin, Diabetes mellitus type 2, Diabetes mellitus, Diabetes mellitus type 1, Obesity, Insulin resistance, Sulfonylurea

113

 To determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.

Concepts: Diabetes mellitus type 2, Diabetes mellitus, Obesity, Anti-diabetic drug, Sulfonylurea, Metformin, Pioglitazone, Thiazolidinedione

66

It is essential to anticipate and limit the social, economic and sanitary cost of type 2 diabetes (T2D), which is in constant progression worldwide. When blood glucose targets are not achieved with diet and lifestyle intervention, insulin is recommended whether or not the patient is already taking hypoglycaemic drugs. However, the benefit/risk balance of insulin remains controversial. Our aim was to determine the efficacy and safety of insulin vs. hypoglycaemic drugs or diet/placebo on clinically relevant endpoints.

Concepts: Insulin, Diabetes mellitus type 2, Diabetes mellitus, Diabetes mellitus type 1, Obesity, Randomized controlled trial, Insulin resistance, Sulfonylurea