Priscilla Hollander

Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes.

OBJECTIVE To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs. RESEARCH DESIGN AND METHODS This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ≥5% weight loss. Secondary end points included achievement of HbA1c <7% (53 mmol/mol), achievement of weight loss ≥10%, and change in HbA1c, waist circumference, fasting blood glucose, and lipids. RESULTS In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m2, and HbA1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (−5.0 vs. −1.8%; P < 0.001) and proportion of patients achieving ≥5% weight loss (44.5 vs. 18.9%, P < 0.001) compared with placebo. NB also resulted in significantly greater HbA1c reduction (−0.6 vs. −0.1% [6.6 vs. 1.1 mmol/mol]; P < 0.001), percent of patients achieving HbA1c <7% (53 mmol/mol) (44.1 vs. 26.3%; P < 0.001), and improvement in triglycerides and HDL cholesterol compared with placebo. NB was associated with higher incidence of nausea (42.3 vs. 7.1%), constipation (17.7 vs. 7.1%), and vomiting (18.3 vs. 3.6%). No difference was observed between groups in the incidence of depression, suicidal ideation, or hypoglycemia. CONCLUSIONS NB therapy in overweight/obese patients with type 2 diabetes induced weight loss, which was associated with improvements in glycemic control and select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.

A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes

OBJECTIVE This trial compared the efficacy and safety profiles of the insulin analogues detemir and glargine as the basal insulin component of a basal-bolus regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated with oral antidiabetic drugs (OADs) or insulin with or without OADs. METHODS This was a multinational, 52-week, openlabel, parallel-group, noninferiority, treat-to-target trial. Patients with a diagnosis of T2DM for > or = 12 months who had been receiving an OAD or insulin, with or without OADs, for > 4 months were randomized in a 2:1 ratio to receive detemir or glargine. According to the approved labeling, detemir could be administered once or twice daily, and glargine was administered once daily. Insulin aspart was given at mealtimes. Insulin secretagogues and a-glucosidase inhibitors were discontinued at study entry, and existing OADs were continued. Doses of detemir and glargine were titrated to achieve a prebreakfast (and predinner for detemir administered twice daily) plasma glucose target of < or = 6.0 mmol/L. Patients monitored their plasma glucose levels before breakfast and dinner on the 3 days before each of 13 scheduled visits, recorded their insulin doses on 1 of these 3 days, and recorded their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and 52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at 52 weeks; secondary efficacy end points included changes in fasting plasma glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at 52 weeks. Safety end points included the frequency of hypoglycemia and adverse events (AEs). RESULTS The intention-to-treat population included 319 patients (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg; mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were receiving insulin and > or = 1 OAD, 35.4 were receiving insulin only, and 18.5% were receiving > or = 1 OAD only. At 52 weeks, there was no significant difference between detemir and glargine in terms of mean HbA(1c) (7.19% and 7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean decrease in HbAlc from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was not significantly affected by whether detemir was administered once or twice daily. There were no significant differences between groups in terms of mean FPG (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92 mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the 10-point SMPG profiles was not significantly different between groups. Mean weight gain at 52 weeks was significantly lower with detemir than with glargine (2.8 vs 3.8 kg; mean difference, -1.04; 95% CI, -2.08 to -0.01; P < 0.05). Doses of basal and prandial insulins at the end of the study were not significantly different between groups. Major hypoglycemic episodes were reported by 4.7% and 5.7% of patients in the respective treatment groups. There was no significant difference in the risk of hypoglycemia between groups. The proportion of patients with AEs and the number of AEs per patient were comparable between groups (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting 377 AEs). CONCLUSIONS when used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. Both basal insulins were associated with clinically relevant reductions in hyperglycemia. Both were well tolerated, with no significant difference in the frequency of hypoglycemia or AEs.

Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension.

Objective: This study investigated the efficacy and safety of insulin degludec (IDeg) once daily (OD), varying injection timing day to day in subjects with type 1 diabetes. Research Design and Methods: This 26-week, open-label, treat-to-target, noninferiority trial compared IDeg forced flexible (Forced-Flex) OD (given in a fixed schedule with a minimum 8 and maximum 40 hours between doses) with IDeg or insulin glargine (IGlar) given at the same time daily OD. In the 26-week extension, all IDeg subjects were transferred to a free-flexible (Free-Flex) regimen, which allowed any-time-of-day dosing, and compared with subjects continued on IGlar. Results: After 26 treatment weeks, mean glycosylated hemoglobin was reduced with IDeg Forced- Flex (−0.40%), IDeg (−0.41%), and IGlar (−0.58%). IDeg Forced-Flex noninferiority was achieved. Fasting plasma glucose reductions were similar with IDeg Forced-Flex and IGlar but greater with IDeg (−2.54 mmol/L) than IDeg Forced-Flex (−1.28 mmol/L) (P = .021). At week 52, IDeg Free-Flex subjects had similar glycosylated hemoglobin but greater fasting plasma glucose reductions than IGlar subjects (−1.07 mmol/L) (P = .005). Confirmed hypoglycemia rates (plasma glucose <3.1 mmol/L or severe hypoglycemia) were similar at weeks 26 and 52. Nocturnal confirmed hypoglycemia was lower with IDeg Forced-Flex vs IDeg (37%; P = .003) and IGlar (40%; P = .001) at week 26 and 25% lower with IDeg Free-Flex vs IGlar (P = .026) at week 52. Conclusions: IDeg can be administered OD at any time of day, with injection timing varied without compromising glycemic control or safety vs same-time-daily IDeg or IGlar. This may improve basal insulin adherence by allowing injection-time adjustment according to individual needs.

Effects of taspoglutide on glycemic control and body weight in obese patients with type 2 diabetes (T-emerge 7 study)†‡§

Therapies that lower blood glucose and provide weight loss may provide meaningful benefits for obese patients with type 2 diabetes mellitus (T2DM). This study assessed the efficacy of taspoglutide compared with placebo on glycemic control and weight in obese patients with T2DM inadequately controlled with metformin monotherapy.

Orlistat in the treatment of obesity.

Orlistat has been well studied in several populations, including patients who do and do not have type 2 diabetes and in patients who have impaired glucose tolerance. Overall, modest, but significant, weight loss was seen in all three groups of patients with favorable effects on the comorbidities of obesity. Orlistat has not been associated with a serious adverse event profile, and the mild GI effects that are seen in some patients are well tolerated. In obese patients who do not have diabetes, weight loss is achieved and maintained as shown in the 2-year studies. Moreover, as was well documented in the Swedish multi-morbidity study, favorable treatment effects on the constituents of the metabolic syndrome are seen. Orlistat, together with a hypocaloric diet, was proven to be effective in preventing diabetes in patients who had impaired glucose tolerance. The addition of orlistat resulted in significant weight loss and significance decreases in levels of HbA1c in patients who had type 2 diabetes who were treated with antihyperglycemic drugs. Studies showed that it is possible to identify early which patients may respond best to treatment. Orlistat offers an attractive treatment option for obese patients who do and do not have diabetes and as a combination drug for treatment of obese patients who have type 2 diabetes.

Impact of an EHR-Based Diabetes Management Form on Quality and Outcomes of Diabetes Care in Primary Care Practices

Health information technology shows promise for improving chronic disease care. This study assessed the impact of a diabetes management form (DMF), accessible within an electronic health record. From 2007 to 2009, 2108 diabetes patients were seen in 20 primary care practices; 1103 visits involved use of the DMF in 2008. The primary outcome was “optimal care”: HbA1c ≤8%, low-density lipoprotein (LDL) cholesterol <100 mg/dL, blood pressure <130/80 mm Hg, not smoking, and aspirin prescription in patients ≥40 years. After adjusting for number of visits, age, sex, and insulin use, DMF-exposed patients showed less improvement in attaining “optimal care” (estimated difference-in-difference [DID] = −2.06 percentage points; P < .001), LDL cholesterol (DID = −2.30; P = .023), blood pressure (DID = −3.05; P < .001), and total cholesterol (DID = −0.47; P = .004) targets. Documented microalbumin tests, aspirin prescription, and eye and foot exams increased more. Thus, DMF use was associated with smaller gains in achieving evidence-based targets, but greater improvement in documented delivery of care.

The case for tight control in diabetes.

PreviewDiabetes mellitus remains one of the most formidable of diseases. Despite great advances in the past half century in the treatment of diabetic complications and their consequences, morbidity and mortality are largely unchanged. Recent evidence indicates that tight control of blood glucose levels is desirable to prevent long-term vascular consequences, although possible risks must be carefully weighed. Dr Hollander examines the issue of tight control and proposes an approach to management of diabetes based on present evidence.

Randomized controlled trial of a nationally available weight control program tailored for adults with type 2 diabetes

Modest weight loss from clinical interventions improves glycemic control in type 2 diabetes (T2DM). Data are sparse on the effects of weight loss via commercial weight loss programs. This study examined the effects on glycemic control and weight loss of the standard Weight Watchers program, combined with telephone and email consultations with a certified diabetes educator (WW), compared with standard diabetes nutrition counseling and education (standard care, SC).

Controversies in prediabetes: do we have a diagnosis?

Abstract It is estimated that more than one–third of US adults exhibit intermediate glycemic control, termed “prediabetes“ or “impaired glucose regulation,” and many individuals with pre–diabetes or diabetes are unaware of their glycemic state. Prediabetes confers significant risks for developing type 2 diabetes mellitus (T2DM) and cardiovascular comorbidities. Early lifestyle intervention and pharmacotherapy have demonstrated success in preventing or delaying onset of T2DM. Thus, early screening and diagnosis of prediabetes, along with subsequent recommendations on preventative measures, are vital in preventing or delaying progression to T2DM. However, a consensus among organizations on the diagnostic criteria defining prediabetes has not been reached, complicating the screening and diagnostic process and resulting in varying subpopulations of patients diagnosed with prediabetes. In this article, the guidelines issued by several organizations are reviewed, as well as recent studies analyzing the predictive value of various diagnostic criteria for the progression to T2DM. Recent trials investigating the effects of lifestyle modification and/or pharmacotherapy on the prevention or delay of development of T2DM have suggested some complex outcomes that require further clarification, but offer some hope for the future. These results, and the varying guidelines for the diagnosis of prediabetes, suggest a need for informed scientific debate on diagnostic criteria and recommendations for preventive care of prediabetic states.

Premixed insulins. How do they compare with other insulin preparations

With the availability of premixed insulins, physicians and diabetic patients have a wider choice of therapeutic options. The premixed preparation now available in the United States consists of 70% NPH insulin and 30% regular insulin. The major advantages of premixed insulins are convenience and improved accuracy. They are suitable for patients who are too impaired to mix their own insulin dose and for those whose mixed-dose ratio is similar to that of the 70/30 preparation.