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Concept: Anti-diabetic drugs

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AIMS: Aside from lowering blood glucose, glucagon-like peptide-1 receptor agonists (GLP-1 RA) attract much attention because of their cardioprotective effects. The aim of this study was to assess the blood pressure-lowering effects of the GLP-1 RAs exenatide and liraglutide compared with other common drugs used to treat type 2 diabetes based on randomised controlled trials including data describing complete blood pressure (BP) changes from baseline. METHODS: We searched the major databases for published or unpublished randomised controlled trials (RCTs) that had been performed in patients with type 2 diabetes and compared the effects of exenatide and liraglutide to those of other common drugs used to treat type 2 diabetes. The RCTs that included data describing BP changes between the baseline and the end of the study were selected for further analysis. RESULTS: A total of 16 RCTs that enrolled 3443 patients in the GLP-1 RA treatment group and 2417 subjects in the control group were included in this meta-analysis. The GLP-1 RA exenatide reduced systolic blood pressure (SBP) when compared with both placebo and insulin glargine, with mean differences of -5.24 mmHg and -3.46 mmHg, respectively, and with 95% confidence intervals (CI) of -6.88 to -3.59, P<0.00001, and -3.63 to -3.29, P<0.00001, respectively. Meanwhile, in the exenatide-treated group, diastolic blood pressure (DBP) was reduced by -5.91 mmHg, with a 95% CI of -7.53 to -4.28, P<0.00001 compared with the placebo group, and -0.99 mmHg with a 95% CI of -1.12 to -0.87, P<0.00001 compared with the sitagliptin group. SBP changes in this meta-analysis were assessed in the groups treated with 1.2 mg or 1.8 mg liraglutide per day. In the 1.2 mg-treated group, liraglutide treatment reduced SBP compared with placebo and glimepiride treatment, with mean differences of -5.60 mmHg and -2.38 mmHg, and 95% CIs of -5.84 to -5.36, P<0.00001 and -4.75 to -0.01, P=0.05, respectively. In the 1.8 mg-treated group, liraglutide also reduced SBP compared with placebo and glimepiride treatment with mean differences of -4.49 mmHg and -2.62 mmHg, and a 95% CI of -4.73 to -4.26, P<0.00001, and -2.91 to -2.33, P<0.00001, respectively. CONCLUSION: Treatment with the GLP-1 RAs exenatide and liraglutide reduced SBP and DBP by 1 to 5 mmHg compared with some other anti-diabetic drugs including insulin, glimepiride and placebo for patients with type 2 diabetes. GLP-1 RAs may offer an alternative therapy for these patients and will help provide extra cardiovascular benefits.

Concepts: Exenatide, Anti-diabetic drug, Glucagon-like peptide-1, Hypertension, Blood pressure, Anti-diabetic drugs, Diabetes mellitus type 2, Diabetes mellitus

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This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents.

Concepts: Anti-diabetic drugs, Obesity, Insulin resistance, Diabetes mellitus type 2

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Hyperglycemia during corticosteroid and asparaginase therapy for acute lymphoblastic leukemia is a significant side effect that is usually treated with insulin. Metformin is an oral antidiabetic biguanide that may cause metabolic acidosis and liver enzyme abnormalities of possible concern in patients receiving chemotherapy.

Concepts: Anti-diabetic drug, Buformin, Glycogen, Phenformin, Diabetes mellitus, Anti-diabetic drugs, Metformin, Acute lymphoblastic leukemia

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Objective: Rapid-acting insulins, including insulin aspart (NovoLog) and lispro (Humalog), do not seem to effectively control postprandial glycemic excursions in children with type 1 diabetes mellitus (T1DM). The objective of this study was to determine if insulin glulisine (Apidra), another rapid-acting insulin analog, would be superior in controlling postprandial hyperglycemia in children with T1DM.Methods: Thirteen prepubertal children ages 4 to 11 years completed this study. Inclusion criteria included T1DM ≥ 6 months, HbA1C 6.9-10%, blood glucose (BG) levels in adequate control for one week prior to study start, multiple daily injections (MDI) with insulin glargine or determir once daily and aspart or lispro pre-meal. If fasting BG was 70-180 mg/dL, subjects received insulin glulisine alternating with aspart prior to a prescribed breakfast with a fixed amount of carbohydrate (45, 60 or 75 grams) for 20 days. Postprandial BG values were obtained at two and four hours.Results: Mean baseline BG values for insulin glulisine (136.4±15.7 mg/dL; mean±SD) and aspart (133.4±14.7 mg/dL) were similar (p=0.34). Mean increase in two-hour postprandial BG was higher in glulisine (+113.5±65.2 mg/dL) than aspart (+98.6±66.9 mg/dL), (p=0.01). BG remained higher at four-hours (glulisine: 141.9±36.5 mg/dL; aspart: 129.0±37.0 mg/dL) (p=0.04). Although statistically insignificant, more hypoglycemic events occurred at two and four-hours postprandial with insulin aspart.Conclusion: Insulin aspart appears to be more effective than insulin glulisine in controlling two and four-hour postprandial BG excursions in prepubertal children with T1DM.

Concepts: Carbohydrate, Diabetes, Diabetes mellitus type 2, Sanofi-Aventis, Anti-diabetic drugs, Blood sugar, Insulin, Diabetes mellitus

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To evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug.

Concepts: Anti-diabetic drugs, Obesity, Insulin resistance, Diabetes mellitus type 2

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To compare the efficacy and safety of new insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).

Concepts: Obesity, Insulin glargine, Insulin therapies, Anti-diabetic drugs, Insulin pump, Insulin, Diabetes mellitus, Diabetes mellitus type 2

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Diabetes is one of the most impactful diseases worldwide. The most commonly prescribed anti-diabetic drug is metformin. In this study, we identified an endosomal Na+/H+ exchanger (NHE) as a new potential target of metformin from an unbiased screen in C. elegans. The same NHE homolog also exists in flies where it too mediates the effects of metformin. Our results suggest that endosomal NHEs could be a metformin target and provide an insight to revealing a novel mechanism of action of metformin on regulating the endocytic cycle.

Concepts: Anti-diabetic drugs, Diabetes mellitus, Pioglitazone, Anti-diabetic drug, Metformin

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Diabetes patients are complex due to considerations of polypharmacy, multimorbidities, medication adherence, dietary habits, health literacy, socioeconomic status, and cultural factors. Meanwhile, insulin and oral hypoglycemic agents are high-alert medications. Therefore it is necessary to require a multidisciplinary team’s integrated endeavors to enhance safe medication management and use of antidiabetic drugs.

Concepts: Anti-diabetic drugs, Anti-diabetic drug, Diabetes mellitus

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The availability of insulin analogs has offered insulin replacement strategies that are proposed to more closely mimic normal human physiology. Specifically, there are a considerable number of reports demonstrating that prandial insulin analogs (lispro, aspart, glulisine) have pharmacokinetic and pharmacodynamic profiles closer to normal, with resulting faster onset and offset of insulin effect when compared with regular human insulin. In addition, basal insulin analogs (glargine, detemir) have been reported to offer longer duration of action, less variability, more predictability, less hypoglycemia (especially nocturnal), and a favorable effect on weight. However, an argument against use of analog insulins as compared with use of regular or NPH insulin is one that states that the effectiveness and risk of hypoglycemia are the only two valid clinical outcomes that should be used to compare the analog and human insulins. Thus, there remains a debate in some circles that analog insulins are no more effective than human insulins, yet at a much higher financial cost. To provide an in-depth understanding of both sides of the argument, we provide a discussion of this topic as part of this two-part point-counterpoint narrative. In the counterpoint narrative presented here, Dr. Davidson provides his argument and defends his opinion that outside of a few exceptions, analog insulins provide no clinical benefit compared with human insulins but cost much more. In the preceding point narrative, Dr. Grunberger provides a defense of analog insulins and their value in clinical management and suggests that when evaluating the “cost” of therapy, a much more global assessment is needed.-William T. CefaluEditor in Chief, Diabetes Care.

Concepts: Diabetes mellitus, Insulin therapies, Human physiology, Anti-diabetic drugs, Eli Lilly and Company, NPH insulin, Effectiveness, Insulin

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Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer’s progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated.

Concepts: Anti-diabetic drugs, Thiazolidinedione, Neurology, Insulin resistance, Insulin, Anti-diabetic drug, Metformin, Diabetes mellitus