The effects of macronutrients composition on hormones and substrates during a meal tolerance test in drugnaive and sitagliptin-treated individuals with type 2 diabetes: a randomized crossover study.

Objective: To evaluate the effect of sitagliptin treatment in early type 2 diabetes mellitus (T2DM) and the impact of different macronutrient compositions on hormones and substrates during meal tolerance tests (MTT). Methods: Half of the drug-naive patients with T2DM were randomly assigned for treatment with 100 mg of sitagliptin, q.d., or placebo for 4 weeks and then submitted to 3 consecutive MTT intercalated every 48 h. The MTTs differed in terms of macronutrient composition, with 70% of total energy from carbohydrates, proteins, or lipids. After 4 weeks of washout, a crossover treatment design was repeated. Both patients and researchers were blinded, and a repeated-measures ANOVA was employed for statistical analysis. Results: Sitagliptin treatment reduced but did not normalize fasting and post-meal glucose values in the three MTTs, with lowered area-under-glucose-curve values varying from 7% to 15%. The sitagliptin treatment also improved the insulinogenic index (+86%) and the insulin/glucose (+25%), glucagon-like peptide-1/glucose (+46%) incremental area under the curves. Patients with early T2DM maintained the lowest glucose excursion after a protein- or lipid-rich meal without any major change in insulin, C-peptide, glucagon, or NEFA levels. Conclusion: We conclude that sitagliptin treatment is tolerable and contributes to better control of glucose homeostasis in early T2DM, irrespective of macronutrient composition. The blood glucose excursion during meal ingestion is minimal in protein- or fat-rich meals, which can be a positive ally for the management of T2DM. Clinical trial no: NCT00881543.

Characteristics Associated with the Choice of First Injectable Therapy Among US Patients With Type 2 Diabetes.

PURPOSE: The objective of this retrospective observational study was to describe and identify clinical and demographic characteristics associated with the choice of first injectable therapy (glucagon-like peptide-1 receptor agonist [GLP-1-RA] or basal insulin) among patients with type 2 diabetes mellitus (T2DM). METHODS: This analysis included adults naive to injectable therapy with T2DM who initiated a GLP-1-RA or basal insulin (index date) between November 2014 and February 2016 using data from the Practice Fusion Electronic Health Record database. Patients with T2DM, ≥1 office visit between 6 and 18 months before the index date, and with ≥1 glycosylated hemoglobin (HbA1c) result in the 6-month preindex (baseline) period were included. A generalized boosted regression model was used to determine the patient characteristics most influential in the selection of a GLP-1-RA or basal insulin as first injectable therapy. Sensitivity analysis was performed by using bootstrapped logistic regression. FINDINGS: The study included 3546 and 7507 GLP-1-RA and basal insulin initiators, respectively. At baseline, GLP-1-RA initiators were significantly younger (mean, 58 vs 63 years), had lower HbA1c values (mean, 8.2% vs 9.1%), lower Diabetes Complications Severity Index (DCSI) scores (mean, 1.0 vs 1.7), and a higher body mass index (BMI) (mean, 36 vs 33 kg/m2) compared with basal insulin initiators. Variables selected by using the generalized boosted regression model with the highest relative importance (≥5%) in the selection of GLP-1-RA or basal insulin were HbA1c level (20.43%), BMI (17.73%), age (12.21%), prior prescription of a sodium-glucose cotransporter-2 inhibitor (9.17%), and DCSI score (8.39%). The same variables, as well as race, were selected by using stepwise logistic regression in all the bootstrapped samples. Patients who were older (adjusted odds ratio [OR], 0.975 [95% CI, 0.971-0.979]) and had higher HbA1c values (OR, 0.741 [95% CI, 0.721-0.761]) and DCSI scores (OR, 0.870 [95% CI, 0.848-0.892]) were significantly less likely to be prescribed a GLP-1-RA compared with basal insulin. Patients with higher BMI (OR, 1.046 [95% CI, 1.040-1.053]) and previous prescription of sodium-glucose cotransporter-2 inhibitors (OR, 2.633 [95% CI, 2.224-2.982]) were significantly more likely to be prescribed a GLP-1-RA. IMPLICATIONS: The clinically relevant differences observed between the 2 patient populations suggest that GLP-1-RAs and basal insulin are prescribed to different types of patients with T2DM. Examining patients' demographic and clinical characteristics may be important in assisting physicians in the choice of patient-centered injectable treatment regimens.

Evidence-based clinical use of insulin premixtures.

Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient's clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil.