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This report presents an algorithm to assist primary care physicians, endocrinologists, and others in the management of adult, nonpregnant patients with type 2 diabetes mellitus. In order to minimize the risk of diabetes-related complications, the goal of therapy is to achieve a hemoglobin A1c (A1C) of 6.5% or less, with recognition of the need for individualization to minimize the risks of hypoglycemia. We provide therapeutic pathways stratified on the basis of current levels of A1C, whether the patient is receiving treatment or is drug naïve. We consider monotherapy, dual therapy, and triple therapy, including 8 major classes of medications (biguanides, dipeptidyl-peptidase-4 inhibitors, incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors, sulfonylureas, meglitinides, and bile acid sequestrants) and insulin therapy (basal, premixed, and multiple daily injections), with or without orally administered medications. We prioritize choices of medications according to safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient adherence, and cost of medications. We recommend only combinations of medications approved by the US Food and Drug Administration that provide complementary mechanisms of action. It is essential to monitor therapy with A1C and self-monitoring of blood glucose and to adjust or advance therapy frequently (every 2 to 3 months) if the appropriate goal for each patient has not been achieved. We provide a flow-chart and table summarizing the major considerations. This algorithm represents a consensus of 14 highly experienced clinicians, clinical researchers, practitioners, and academicians and is based on the American Association of Clinical Endocrinologists/American College of Endocrinology Diabetes Guidelines and the recent medical literature.

The prevalence of type 2 diabetes mellitus continues to increase in many Asian countries, with possible contributing factors, such as younger‐onset disease, diabetes development at lower body mass index, higher visceral fat accumulation and poorer β‐cell function, among Asian populations. Sodium–glucose cotransporter 2 inhibitors have been shown to confer favorable effects in type 2 diabetes mellitus patients, such as improved glycemic control, weight and blood pressure reduction, and importantly, cardiorenal benefits. Sodium–glucose cotransporter 2 inhibitors are generally well‐tolerated, and have a well‐defined safety profile based on evidence from numerous clinical trials and post‐marketing pharmacovigilance reporting. To our knowledge, this review is the first to provide a comprehensive coverage of the adverse events of sodium–glucose cotransporter 2 inhibitors, as well as their management and counseling aspects for Asian type 2 diabetes mellitus populations. Sodium glucose co‐transporter‐2 (SGLT‐2) inhibitor have gained a central role in the treatment of type 2 diabetes mellitus particularly owing to its cardiorenal benefits. It is generally well‐tolerated and have a well‐defined safety profile. This review is the first to provide a comprehensive coverage on the side effects of SGLT2i as well as their management and counseling aspects for Asian type 2 diabetes mellitus population.

The pathophysiology of type 2 diabetes mellitus is complex and involves multiple organs and hormones, suggesting that successful treatment may require therapies that target multiple mechanisms. Exenatide, a glucagon-like peptide 1 receptor agonist, has a multifaceted mechanism of action involving pancreatic α and β cells, hepatic glucose production, gastric motility, and satiety. Exenatide once weekly (a twice-daily formulation is also available) utilizes continuous release from biodegradable microspheres. This review discusses relevant efficacy and tolerability outcomes with exenatide once weekly in the context of its pharmacology. The medical literature was searched to identify relevant data on the pharmacology and clinical effects of exenatide once weekly. Exenatide once weekly, like the twice-daily formulation, has been shown to improve glycemic parameters, promote weight loss, result in beneficial changes in cardiovascular risk factors, and is well-tolerated. The characteristics of exenatide once weekly make it a treatment option for patients with type 2 diabetes.

The objectives of this clinical practice guidelines (CPG) are to provide: An education resource for the development of a comprehensive care plan for clinical endocrinologists and other clinicians who care for patients with DM. An evidence-based resource developed in 2011 addressing specific problems in DM care. A document that can eventually be implemented electronically in clinical practices to assist with decision-making for patients with DM. This CPG focuses on comprehensive care and practical implementation strategies in a more concise format than could be achieved by an encyclopedic citation of all pertinent primary references. The AACE Board of Directors mandated a new CPG for the development of a DM comprehensive care plan. This CPG was developed in accordance with the AACE Protocol for Standardized Production of Clinical Practice Guidelines-2010 Update. This CPG has been reviewed and approved by the primary writers, other invited experts, the AACE Publications Committee, and the AACE Board of Directors before submission for peer review by Endocrine Practice.

Type 2 diabetes mellitus (DM) is a prevalent disorder that affects children, adolescents, and adults worldwide. In addition to risks of microvascular disease, patients with type 2 DM often have multiple risk factors of macrovascular disease; for example, approximately 90% of patients with type 2 DM are overweight/obese. Type 2 DM is a complex disease that involves a variety of pathophysiologic abnormalities, including insulin resistance, increased hepatic glucose production, and abnormalities in the secretion of hormones, such as insulin, glucagon, amylin, and incretins. Incretins are gut-derived peptides with a variety of glucoregulatory functions. Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. Treatment with GLP-1 receptor agonists has demonstrated durable glycemic control and improvement in multiple cardiovascular disease risk factors. In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. These factors should be considered when selecting monotherapy or elements of combination therapy for patients with type 2 DM who are overweight/obese, for patients who have experienced hypoglycemia with other agents, and when achieving glycemic targets is difficult.

To determine the effect of mild renal impairment (RI) on the efficacy and safety of liraglutide in patients with type 2 diabetes mellitus. In this meta-analysis, we examined the 6 LEAD (Liraglutide Effect and Action in Diabetes) studies. Data from patients with type 2 diabetes who had normal renal function, mild RI, or moderate or severe RI were pooled for analysis. Renal function was measured by creatinine clearance as determined by the Cockcroft-Gault equation: normal renal function = creatinine clearance >89 mL/min; mild RI = 60 mL/min ≤ creatinine clearance ≤ 89 mL/min; and moderate or severe RI = creatinine clearance <60 mL/min. The meta-analysis included patients administered once-daily liraglutide (1.2 or 1.8 mg) or placebo as either monotherapy or in combination with oral antidiabetic drugs for 26 weeks. In addition, a pooled analysis of all phase 2 and 3 liraglutide trials was done to examine rates of altered renal function. Mild RI did not affect the estimated treatment differences in hemoglobin A1c. Patients with normal renal function demonstrated decreases in body weight and systolic blood pressure with either dosage of liraglutide, whereas patients in either RI group also demonstrated a decrease in body weight and systolic blood pressure, but these differences were not significant compared with differences observed in the placebo group. Liraglutide treatment vs placebo was safe and well tolerated in patients with mild RI, as there were no significant differences in rates of renal injury, minor hypoglycemia, or nausea. A trend towards increased nausea was observed in patients with moderate or severe RI receiving liraglutide, although the number of patients in this treatment group was too low to determine significance. Mild RI, as determined by the Cockcroft-Gault equation, had no effect on the efficacy and safety of liraglutide in this meta-analysis.

Type 2 diabetes is characterized by agradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of post-prandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) to guide management The objectives of this article are to review current data on postprandial hyperglycemia and to assess whether, and how, management of type 2 diabetes should change to reflect new clinical findings. Articles were selected from MEDLINE searches (key words: postprandial glucose, postprandial hyperglycemia, and cardiovascular disease) and from our personal reference files, with emphasis on the contribution of postprandial hyperglycemia to overall glycemic load or cardiovascular (CV) risk. About 33% of people diagnosed as having type 2 diabetes based on postprandial hyperglycemia have normal FPG. PPG contributes ≥70% to the total glycemic load in patients who are fairly well controlled (HbA, 1c ≤.3%). Furthermore, there is a linear relationship between the risk of CV death and the 2-hour oral glucose tolerance test (OGTT). Increased mortality is evident at OGTT levels of ∼90 mg/dL (5 mmol/L), which is well below current definitions of type 2 diabetes. Biphasic insulin aspart was shown to be more effective at reducing HbAlc below currently recommended levels than basal insulin glargine (66% vs 40%; P < 0.001), and it reduced endothelial dysfunction more effectively than regular insulin ( P < 0.01). Repaglinide achieved regression of carotid atherosclerosis (intima-media thickness) in 52% of patients versus 18 % for glyburide ( P < 0.01) over 1 year, although levels of HbAlc and CV risk factors were similar for both treatment groups. Finally, acarbose reduced the relative risk of CV events by 49% over 3.3 years versus placebo in patients with impaired glucose tolerance (2.2% vs 4.7%; P = 0.03) and by 35% over ≥1 year in patients with type 2 diabetes (9.4% vs 6.1%; P = 0.006). All components of the glucose triad (ie,FPG, HbA 1c, and PPG) should be considered in the management of type 2 diabetes. Therapy targeted at PPG has been shown to improve glucose control and to reduce the progression of atherosclerosis and CV events; therefore, physicians should consider monitoring and targeting PPG, as well as HbA lc and FPG, in patients with type 2 diabetes.

Background: Insulin is recommended as a second-line treatment after diet and metformin fail to reach and/or maintain glycemic targets considered to minimize the risk for long-term diabetic complications. Hypoglycemia and the fear of developing hypoglyce-mia, however, remain substantial barriers to the initiation and optimal use of insulin. Objective: The aim of this study was to compare biphasic insulin aspart 30 (BIAsp 30) with biphasic human insulin 30 (BHI 30) with respect to glycemic control and the risk for hypoglycemia using a meta-analysis of clinical trials comparing these insulins in patients with type 2 diabetes mellitus (T2DM). Methods: We included all published and unpublished, randomized, controlled trials in adult patients with T2DM (treatment duration ≥12 weeks) for which individual patient data were available. All clinical databases and local trial registries of Novo Nordisk A/S (Soeborg, Denmark) were searched to identify clinical trials comparing the 2 products. The predefined primary end point of the study was the overall rate of nocturnal hypoglyce-mia (major, minor, and symptoms-only hypoglycemia occurring from 12:00–6:00 AM). Hypoglycemia was analyzed using a negative binomial distribution model, accounting for exposure time. Glycemic end points were analyzed at 12 to 16 weeks of treatment using ANCOVA, adjusting for baseline. Secondary safety end points were the rates of major hypoglycemia (hypoglycemia requiring third-party assistance), minor hypoglycemia (symptoms confirmed by plasma glucose [PG] <3.1 mmol/L), daytime hypoglycemia (major, minor, and symptoms-only hypoglycemia occurring from 6:01 AM–11:59 PM), overall hypoglycemia (the sum of all major, minor, and symptoms-only episodes), and change in weight from baseline to 12 to 16 weeks of treatment. Secondary efficacy end points were changes in glycosylated hemoglobin (HbA 1c), fasting PG (FPG), postprandial PG increment (averaged over breakfast, lunch, and dinner), and insulin dose. Results: Nine randomized, parallel or crossover trials were included (N = 1674; male sex, 57%; mean [SD] age, 61.0 [10.6] years; body mass index, 26.7 [4.6] kg/m 2; HbA 1c, 8.1% [1.4%]; duration of diabetes, 10.9 [7.9] years). Rates of overall hypoglycemia were not significantly different (rate ratio [RR] = 1.08; 95% CI, 0.94–1.24; P = NS) between treatments. BIAsp 30 had a 50% lower rate of nocturnal hypoglycemia than BHI 30 (RR = 0.50; 95% CI, 0.38–0.67; P < 0.01), whereas the rate of daytime hypoglycemia was 24% lower for BHI 30 (RR = 1.24; 95% CI, 1.08–1.43; P < 0.01). The likelihood of major hypo-glycemia was significantly lower with BIAsp 30 compared with BHI 30 (odds ratio = 0.45; 95% CI, 0.22–0.93; P < 0.05). BIAsp 30 was associated with reduced PPG increment (averaged over breakfast, lunch and dinner) compared with BHI 30 (treatment difference, −0.31; 95% CI, −0.49 to −0.07; P < 0.01). There was a significantly larger reduction in FPG associated with BHI 30 (treatment difference, 0.63; 95% CI, 0.31–0.95; P < 0.01). However, no significant treatment difference was found for HbA 1c (treatment difference, 0.04; 95% CI, −0.02 to 0.10; P = NS). Conclusion: This meta-analysis found BIAsp 30 to be associated with a significantly lower rate of nocturnal and major hypoglycemia, but a significantly increased risk for daytime hypoglycemia, compared with BHI 30 at a similar level of HbA 1c in patients with T2DM.

The American Association of Clinical Endocrinologists/American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. Researchers have encouraged medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources, and individual patient circumstances.