Safety of sodium-glucose cotransporter 2 inhibitors in Asian type 2 diabetes populations.

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 ß-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.

The status of diabetes and its complications in Latin-American population: A review article.

The Latino population consists of distinct cultural groups, with differences in dietary habits and lifestyle that can affect the risk for type 2 diabetes. The best terminology today is Latino/Hispanic, and it should only be used as ethnicity. Latin-America has different races such as Caucasians, Native Americans, Blacks and Asians, and many mixtures of all. The leading cause of death in Latin-America is Cardiovascular diseases and the most important risk factor is diabetes mellitus (DM). According to the latest estimates from the Global Burden of Disease, the burden of DM was greater than expected in Latin America and the Caribbean region. Extensive data illustrates that lower cardiovascular disease risk in Latino group is a paradox. Instead, it is evident that the cardiovascular disease is the leading cause of mortality in Latinos.

Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data.

BACKGROUND: To examine the impact on glycemic control of achieving postprandial glucose (PPG) target with lixisenatide, a once-daily glucagon-like peptide-1 receptor agonist approved in the US, in patients with uncontrolled type 2 diabetes (T2D) on basal insulin, an agent that primarily targets fasting plasma glucose. METHODS: A post hoc pooled analysis was conducted using clinical trial data extracted from the intent-to-treat subpopulation of patients with T2D who participated in the 24-week, phase 3, randomized, double-blind, placebo-controlled, 2-arm parallel-group, multicenter GetGoal-L (NCT00715624), GetGoal-Duo 1 (NCT00975286) and GetGoal-L Asia trials (NCT00866658). RESULTS: Data from 587 lixisenatide-treated patients and 484 placebo-treated patients were included. Patients on lixisenatide were more likely to achieve a PPG target of < 10 mmol/L (< 180 mg/dL) than placebo-treated patients (P < 0.001), regardless of baseline fasting plasma glucose (FPG) levels. More importantly, those who reached the PPG target experienced a significantly greater reduction in mean HbA1c, were more likely to achieve HbA1c target of < 53 mmol/mol (< 7.0%), and experienced weight loss. Those outcomes were achieved with no significant differences in the risk of symptomatic hypoglycemia compared with placebo. CONCLUSION: Compared with placebo, addition of lixisenatide to basal insulin improved HbA1c and reduced PPG, without increasing hypoglycemia risk. These findings highlight the importance of PPG control in the management of T2D, and provide evidence that adding an agent to basal insulin therapy that also impacts PPG has therapeutic value for patients who are not meeting glycemic targets. TRIAL REGISTRATION: NCT00715624. Registered 15 July 2008, NCT00975286. Registered 11 September 2009, NCT00866658. Registered 20 March 2009.

TRANSCULTURAL DIABETES CARE IN THE UNITED STATES - A POSITION STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS.

The American Association of Clinical Endocrinologists (AACE) has created a transculturalized diabetes chronic disease care model that is adapted for patients across a spectrum of ethnicities and cultures. AACE has conducted several transcultural activities on global issues in clinical endocrinology and completed a 3-city series of conferences in December 2017 that focused on diabetes care for ethnic minorities in the U.S. Proceedings from the "Diabetes Care Across America" series of transcultural summits are presented here. Information from community leaders, practicing health care professionals, and other stakeholders in diabetes care is analyzed according to biological and environmental factors. Four specific U.S. ethnicities are detailed: African Americans, Latino/Hispanics, Asian Americans, and Native Americans. A core set of recommendations to culturally adapt diabetes care is presented that emphasizes culturally appropriate terminology, transculturalization of white papers, culturally adapting clinic infrastructure, flexible office hours, behavioral medicine-especially motivational interviewing and building trust-culturally competent nutritional messaging and health literacy, community partnerships for care delivery, technology innovation, clinical trial recruitment and retention of ethnic minorities, and more funding for scientific studies on epigenetic mechanisms of cultural impact on disease expression. It is hoped that through education, research, and clinical practice enhancements, diabetes care can be optimized in terms of precision and clinical outcomes for the individual and U.S. population as a whole.

SGLT2 inhibitors in patients with type 2 diabetes and renal disease: overview of current evidence.

Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and is associated with poor clinical outcomes, including an increased risk of all-cause and cardiovascular mortality, as well as adverse economic and social effects. Slowing the development and progression of CKD remains an unmet clinical need in patients with T2DM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are widely used for the management of T2DM and have effects beyond glucose lowering that include cardiovascular benefits and potential renoprotective effects. Although the glucose-lowering efficacy of these agents is dependent on renal function, the cardiovascular and renal benefits of SGLT2 inhibition appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m2. Clinical evidence has indicated that these agents can reduce the risk of development or worsening of albuminuria, a marker of renal damage, through a range of mechanisms. These include blood pressure lowering, reduction of intraglomerular pressure and hyperfiltration, modification of inflammatory processes, reduction of ischemia-related renal injury, and increases in glucagon levels. The blood pressure-lowering effect of SGLT2 inhibitors is maintained in people with CKD and could further contribute to reduced renal burden, as well as potentially offering synergistic effects with antihypertensive therapies in these patients. Several cardiovascular outcomes trials (CVOTs) have included renal endpoints, adding to the growing evidence of the potential renoprotective effects of these agents in patients with T2DM. Several ongoing dedicated renal outcomes trials will provide further guidance on the potential clinical role of SGLT2 inhibitors in slowing the development and progression of renal impairment in individuals with T2DM.

Albiglutide efficacy and safety in the Latino/Hispanic subpopulation for the integrated phase III program.

OBJECTIVE: to evaluate the efficacy and safety of albiglutide compared with placebo and active comparators from an integrated trial subpopulation of Latino/Hispanic patients whose type 2 diabetes mellitus (T2DM) was inadequately controlled on their current regimen of diet and exercise, with or without oral antidiabetic drugs (OADs) and/or insulin. METHODS: Latino/Hispanic patient subpopulations (N = 1204) across 7 phase III albiglutide studies (N = 4400) were evaluated post-hoc for efficacy and safety. Comparators were placebo, sulfonylureas, insulin, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors. Glycatedhemoglobin (HbA1c) change from baseline to the time of the primary endpoint assessment (from 26 to 104 weeks) was evaluated in patients on diet and exercise and/or OADs, with or without insulin. Patients were allowed to continue in the study if hyperglycemic rescue was required, according to a prespecified algorithm and at the discretion of the investigator. RESULTS: At baseline in the Latino/Hispanic subpopulation, the mean HbA1c was 8.3%, mean age was 53 years, mean body mass index was 32 kg/m2, and mean duration of T2DM was 8.0 years. The primary endpoint of mean HbA1c difference (albiglutide - placebo) was -0.94% for the Latino/Hispanic subpopulation and -0.86% (p < 0.001) for the overall phase III population. Changes in fasting plasma glucose mirrored those of HbA1c. Weight loss with albiglutide was numerically greater than with OADs and insulin in both populations, but it was smaller than with liraglutide. Within the Latino/Hispanic subpopulation, more injection-site reactions were reported with albiglutide vs all comparators, while gastrointestinal and hypoglycemic adverse events were comparable between the two groups, and the latter was uncommon when used without insulin and/or a sulfonylurea. CONCLUSIONS: In the Latino/Hispanic population, albiglutide resulted in effective lowering of glucose and modest weight loss, and it was generally well tolerated.

Dapagliflozin suppresses glucagon signaling in rodent models of diabetes.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose. In these type 1 diabetic rats, glucose stimulated glucagon secretion by alpha cells; this was prevented by dapagliflozin. Two models of type 2 diabetes, severely diabetic Zucker rats and db/db mice fed dapagliflozin, showed significant improvement of blood glucose levels and glucose disposal, with reduced evidence of glucagon signaling in the liver, as exemplified by reduced phosphorylation of hepatic cAMP-responsive element binding protein, reduced expression of phosphoenolpyruvate carboxykinase 2, increased hepatic glycogen, and reduced hepatic glucose production. Plasma glucagon levels did not change significantly. However, dapagliflozin treatment reduced the expression of the liver glucagon receptor. Dapagliflozin in rodents appears to lower blood glucose levels in part by suppressing hepatic glucagon signaling through down-regulation of the hepatic glucagon receptor.

Resolving the KgA1c paradox in the management of type 2 diabetes mellitus.

Excess body weight is a leading cause of metabolic complications such as hypertension and dyslipidemia in T2DM patients. Available antihyperglycemic agents have minimal or no impact on these complications and a majority are known to trigger weight gain, thereby exerting a paradoxical effect on overall metabolic status. This review introduces the concept of 'KgA1c paradox' and underscores the significance of resolving this paradox for comprehensive T2DM management. It provides a therapeutic rationale for inclusion of sodium glucose cotransporter 2 inhibitors in the T2DM treatment algorithm as these agents have demonstrated favorable glycemic effects along with reduction in body weight.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE DYSFUNCTION.

This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

Effects of once-weekly dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials.

Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes (T2D). Integrated data from 9 phase II and III trials in people with T2D (N = 6005) were used to evaluate the effects of dulaglutide on estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR) and kidney adverse events (AEs). No significant differences in eGFR were observed during treatment for dulaglutide vs placebo, active comparators or insulin glargine (mean ± standard deviation values: dulaglutide vs placebo: 87.8 ± 17.7 vs 88.2 ± 17.9 mL/min/1.73 m2 , P = .075; dulaglutide vs active comparators: 89.9 ± 16.7 vs 88.8 ± 16.3 mL/min/1.73 m2 , P = .223; and dulaglutide vs insulin glargine: 85.9 ± 18.2 vs 83.9 ± 18.6 mL/min/1.73 m2 , P = .423). Lower UACR values were observed for dulaglutide vs placebo, active comparators and insulin glargine (at 26 weeks, median [Q1-Q3] values were: dulaglutide vs placebo: 8.0 [4.4-20.4] vs 8.0 [4.4-23.9] mg/g, P = .023; dulaglutide vs active comparators: 8.0 [4.4-21.2] vs 8.9 [4.4-27.4] mg/g, P = .013; and dulaglutide vs insulin glargine: 8.9 [4.4-29.2] vs 12.4 [5.3-50.5] mg/g, P = .029). AEs reflecting potential acute renal failure were 3.4, 1.7 and 7.0 events/1000 patient-years for dulaglutide, active comparators and placebo, respectively. In conclusion, dulaglutide treatment of clinical trial participants with T2D did not affect eGFR and slightly decreased albuminuria.

Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of Type 2 Diabetes: An Overview.

Metformin is recommended as a first-line therapy for patients with type 2 diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals with metformin monotherapy and require subsequent combination therapy with other antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood glucose, initial combination therapy may be required to achieve glycemic control. The American Association for Clinical Endocrinologists algorithm for the treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 (SGLT2) inhibitor as the first oral combination in patients who present with HbA1c ≥7.5%. Canagliflozin, an SGLT2 inhibitor, lowers the renal threshold for glucose and increases urinary glucose excretion leading to a mild osmotic diuresis and a net caloric loss. The effect of canagliflozin is insulin-independent and complementary to other AHAs, including metformin. A fixed-dose combination (FDC) of canagliflozin and metformin is also available with variable dosing, which may be attractive to some patients owing to the potential for reduced pill burden and costs. This article reviews the efficacy and safety of canagliflozin in combination with metformin based on data from the canagliflozin phase 3 clinical program. As initial combination therapy in drug-naïve patients or as dual therapy with metformin or triple therapy in combination with metformin and other AHAs, canagliflozin 100 and 300 mg improved glycemic control and provided reductions in body weight and systolic blood pressure that were sustained for up to 104 weeks. Canagliflozin was generally well tolerated across studies in combination with metformin. An increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic infections, urinary tract infections, osmotic diuresis-related AEs) was observed with canagliflozin. Canagliflozin was associated with a low incidence of hypoglycemia when not used in conjunction with AHAs associated with hypoglycemia (i.e., insulin or sulfonylurea). Together, these results support the use of a canagliflozin and metformin FDC as a treatment approach for a broad range of patients with T2DM. FUNDING: Janssen Scientific Affairs, LLC.

EFFICACY AND SAFETY OF DULAGLUTIDE IN HISPANIC/LATINO PATIENTS WITH TYPE 2 DIABETES IN THE AWARD CLINICAL PROGRAM.

OBJECTIVE: The aim of this post hoc analysis was to assess the efficacy and safety of once-weekly dulaglutide in Hispanic/Latino patients with type 2 diabetes (T2D) in phase 3 AWARD trials 1 to 6. METHODS: Hispanic/Latino data at Week 26 were pooled across studies for each dulaglutide dose to analyze the change from baseline in glycosylated hemoglobin (HbA1c), percent to HbA1c goal, and adverse events (AEs). Change from baseline in HbA1c, change from baseline in weight and hypoglycemia were analyzed by Hispanic/Latino and non-Hispanic/Latino subgroups for each study. RESULTS: Of the 3,136 patients randomized to dulaglutide 1.5 or 0.75 mg, 949 were reported as having Hispanic/Latino ethnicity. Baseline characteristics were similar for Hispanic/Latino and overall populations, except there were slightly more Hispanic/Latino females and weight was slightly lower for Hispanic/Latino patients. Hispanic/Latino patients receiving dulaglutide 1.5 mg had a reduction in HbA1c of 1.25% (95% confidence interval [CI]: -1.35, -1.15); dulaglutide 0.75 mg had a reduction of 1.07% (95% CI: -1.18, -0.96). Reductions in HbA1c and percent to goal HbA1c <7% and ≤6.5% were similar between Hispanic/Latino patients and the overall population. Weight change and hypoglycemia were similar between Hispanic/Latino and non-Hispanic/Latino subgroups for all studies. Treatment-emergent AEs were consistent with the overall population. CONCLUSION: Dulaglutide improved glycemic control with the potential for weight loss in Hispanic/Latino patients with T2D. Dulaglutide was well tolerated and had a low risk of hypoglycemia when used without insulin secretagogues or insulin. In the Hispanic/Latino population, dulaglutide efficacy and safety was consistent with that of the overall population. ABBREVIATIONS: AE = adverse event AWARD = Assessment of Weekly AdministRation of dulaglutide in Diabetes BID = twice daily CARMELA = The Cardiovascular Risk Factor Multiple Evaluation of Latin America CI = confidence interval GLP-1 RA = glucagon-like peptide-1 receptor agonist HbA1c = glycosylated hemoglobin T2D = type 2 diabetes.

Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes.

OBJECTIVES: To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks. METHODS: Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction ≥5% at Week 52 were evaluated. Safety was assessed based on adverse event reports. RESULTS: Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction ≥5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated. CONCLUSIONS: A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.

TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.

Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

OBJECTIVE: To assess the efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in patients of different ethnicities. DESIGN SETTING AND PATIENTS: Post hoc analysis of data pooled from four randomized, placebo-controlled, phase 3 studies of adults with inadequately controlled type 2 diabetes mellitus (T2DM). INTERVENTIONS: Once daily oral canagliflozin 100 mg or 300 mg, or placebo. MAIN OUTCOME MEASURES: Efficacy endpoints included change from baseline in HbA1c, body weight (BW), systolic blood pressure (SBP), and lipids at week 26; safety and tolerability were assessed by adverse event reports. RESULTS: Of the 2,313 patients included in this pooled analysis, 609 self-identified as Hispanic/Latino. Hispanic/Latino patients had a mean age of 54 years, mean duration of T2DM of 7 years, mean HbA1c of 8.1%, mean body mass index of 31.2 kg/m(2), and mean SBP of 126.1 mm Hg. There were more women in the non-Hispanic/Latino cohort (63%) compared with the Hispanic/Latino cohort. Placebo-subtracted changes in HbA1c were -.82% with canagliflozin 100 mg and -.94% with canagliflozin 300 mg in the Hispanic/Latino cohort, which were similar to reductions observed in the non-Hispanic/Latino cohort. Significantly greater dose-related reductions in HbA1c, BW, and SBP were observed with both canagliflozin doses compared with placebo. Canagliflozin was generally well-tolerated. Genital mycotic infections were less frequent in Hispanic/Latino women than in non-Hispanic/Latino women. CONCLUSIONS: The SGLT2 inhibitor canagliflozin was generally well-tolerated and was associated with clinically meaningful reductions in HbA1c, BW, and SBP in both Hispanic/Latino and non-Hispanic/Latino patients with T2DM.

Impact of CMS Competitive Bidding Program on Medicare Beneficiary Safety and Access to Diabetes Testing Supplies: A Retrospective, Longitudinal Analysis.

OBJECTIVE: In 2011, the Centers for Medicare & Medicaid Services (CMS) launched the Competitive Bidding Program (CBP) in nine markets for diabetes supplies. The intent was to lower costs to consumers. Medicare claims data (2009-2012) were used to confirm the CMS report (2012) that there were no disruptions in acquisition caused by CBP and no changes in health outcomes. RESEARCH DESIGN AND METHODS: The study population consisted of insulin users: 43,939 beneficiaries in the nine test markets (TEST) and 485,688 beneficiaries in the nontest markets (NONTEST). TEST and NONTEST were subdivided: those with full self-monitoring of blood glucose (SMBG) supply acquisition (full SMBG) according to prescription and those with partial/no acquisition (partial/no SMBG). Propensity score-matched analysis was performed to reduce selection bias. Outcomes were impact of partial/no SMBG acquisition on mortality, inpatient admissions, and inpatient costs. RESULTS: Survival was negatively associated with partial/no SMBG acquisition in both cohorts (P < 0.0001). Coterminous with CBP (2010-2011), there was a 23.0% (P < 0.0001) increase in partial/no SMBG acquisition in TEST vs. 1.7% (P = 0.0002) in NONTEST. Propensity score-matched analysis showed beneficiary migration from full to partial/no SMBG acquisition in 2011 (1,163 TEST vs. 605 NONTEST) was associated with more deaths within the TEST cohort (102 vs. 60), with higher inpatient hospital admissions and associated costs. CONCLUSIONS: SMBG supply acquisition was disrupted in the TEST population, leading to increased migration to partial/no SMBG acquisition with associated increases in mortality, inpatient admissions, and costs. Based on our findings, more effective monitoring protocols are needed to protect beneficiary safety.

Exenatide Once Weekly: A Review of Pharmacology and Treatment Considerations in Type 2 Diabetes.

PURPOSE: 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 ß 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. METHODS: The medical literature was searched to identify relevant data on the pharmacology and clinical effects of exenatide once weekly. FINDINGS: 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. IMPLICATIONS: The characteristics of exenatide once weekly make it a treatment option for patients with type 2 diabetes.

CLINICAL AND COST-EFFECTIVENESS OF INSULIN DELIVERY WITH V-GO(®) DISPOSABLE INSULIN DELIVERY DEVICE VERSUS MULTIPLE DAILY INJECTIONS IN PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTROLLED ON BASAL INSULIN.

OBJECTIVE: To compare two methods of delivering intensified insulin therapy (IIT) in patients with type 2 diabetes inadequately controlled on basal insulin ± concomitant antihyperglycemic agents in a real-world clinical setting. METHODS: Data for this retrospective study were obtained using electronic medical records from a large multicenter diabetes system. Records were queried to identify patients transitioned to V-Go(®) disposable insulin delivery device (V-Go) or multiple daily injections (MDI) using an insulin pen to add prandial insulin when A1C was >7% on basal insulin therapy. The primary endpoint was the difference in A1C change using follow-up A1C results. RESULTS: A total of 116 patients were evaluated (56 V-Go, 60 MDI). Both groups experienced significant glycemic improvement from similar mean baselines. By 27 weeks, A1C least squares mean change from baseline was -1.98% (-21.6 mmol/mol) with V-Go and -1.34% (-14.6 mmol/mol) with MDI, for a treatment difference of -0.64% (-7.0 mmol/mol; P = .020). Patients using V-Go administered less mean ± SD insulin compared to patients using MDI, 56 ± 17 units/day versus 78 ± 40 units/day (P<.001), respectively. Diabetes-related direct pharmacy costs were lower with V-Go, and the cost inferential from baseline per 1% reduction in A1C was significantly less with V-Go ($118.84 ± $158.55 per patient/month compared to $217.16 ± $251.66 per patient/month with MDI; P = .013). CONCLUSION: Progression to IIT resulted in significant glycemic improvement. Insulin delivery with V-Go was associated with a greater reduction in A1C, required less insulin, and proved more cost-effective than administering IIT with MDI. ABBREVIATIONS: A1C = glycated hemoglobin ANCOVA = analysis of covariance CI = confidence interval CSII = continuous subcutaneous insulin infusion FPG = fasting plasma glucose IIT = intensified insulin therapy LSM = least squares mean MDI = multiple daily injections T2DM = type 2 diabetes mellitus TDD = total daily dose.

Glucagon therapeutics: Dawn of a new era for diabetes care.

Although insulin monotherapy prevents death from ketoacidosis, it does not prevent either the hyperglycemic surges or the hypoglycemic plunges of glucose levels that plague the majority of patients with type 1 diabetes. However, significant improvements have occurred with the combination of continuous insulin delivery matched by continuous glucose monitoring, but the technology is not available for all patients, requires extensive education, is expensive and moreover, while much better than standard care, it almost never reduces haemoglobin A1c (HbA1c ) to below 6%. This may indicate that an improved diabetes therapy involving antagonism of glucagon action will for the first time control glucose levels to normal and eradicate the long-term complications of diabetes. Although one can never predict that results in animals will be reproduced in humans, the available evidence suggests that patients with type 1 and type 2 diabetes may expect far superior control of the metabolic abnormalities without the need for significant monitoring of glucose, a very important but expensive part of any insulin regimen.