Newer oral and noninsulin therapies to treat type 2 diabetes mellitus

Hermayer, Kathie L.; Dake, Andrew W.

doi:10.3949/ccjm.83.s1.04

Cited by 5 publications

(10 citation statements)

References 41 publications

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“…[7][8][9] GLP-1RAs have glucose-dependent antidiabetic effects, and the risk of hypoglycaemia is comparatively low. [10][11][12] They also inhibit glucagon secretion from pancreatic α cells, thereby inhibiting abnormal hepatic glycogen output. [10][11][12] GLP-1RAs reduce gastrointestinal motility and inhibit central appetite, thereby reducing food intake and body weight.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] They also inhibit glucagon secretion from pancreatic α cells, thereby inhibiting abnormal hepatic glycogen output. [10][11][12] GLP-1RAs reduce gastrointestinal motility and inhibit central appetite, thereby reducing food intake and body weight. [10][11][12] Furthermore, animal experiments showed that GLP-1 promotes the proliferation of pancreatic β cells and inhibits β cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] GLP-1RAs reduce gastrointestinal motility and inhibit central appetite, thereby reducing food intake and body weight. [10][11][12] Furthermore, animal experiments showed that GLP-1 promotes the proliferation of pancreatic β cells and inhibits β cell apoptosis. 13 In addition, GLP-1RAs displayed cardioprotective effects and also protected endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

Gao

Zhang

et al. 2020

Diabetes Obesity Metabolism

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Aim: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D). Materials and methods: This was a multicentre, randomized, double-blind, placebocontrolled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. Results: The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (−1.16% [0.08%] and −1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred. Conclusion: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

Gao

Zhang

et al. 2020

Diabetes Obesity Metabolism

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“…In the USA, nearly 50% of patients with type 2 diabetes (T2D) are living with uncontrolled hyperglycemia [1,2], despite the introduction of numerous new diabetes medications over the past two decades [3,4]. A retrospective analysis of US claims data from 1.66 million patients with T2D showed a declining trend (from 56.4% in 2006 to 54.2% in 2013; p \ 0.001) in patients achieving a glycated hemoglobin (HbA1c) target of \ 7.0%.…”

Section: Introductionmentioning

confidence: 99%

Impact of Simultaneous Versus Sequential Initiation of Basal Insulin and Glucagon-like Peptide-1 Receptor Agonists on HbA1c in Type 2 Diabetes: A Retrospective Observational Study

et al. 2020

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Introduction: When and how to intensify treatment in patients with type 2 diabetes (T2D) not achieving glycated hemoglobin (HbA1c) targets with oral antidiabetic drugs (OADs) in clinical practice remains a matter of clinical preference. This pilot study was conducted using the retrospective observational data from such patients to evaluate the impact on HbA1c of three treatment sequences: simultaneous initiation of basal insulin (BI) and a glucagonlike peptide-1 receptor agonist (GLP-1 RA; Cohort 1); BI followed by GLP-1 RA initiation within a 90-day timeframe (Cohort 2); or BI followed by GLP-1 RA initiation beyond 90 days (Cohort 3). Methods: Data from the regional US electronic medical records database, Research Action for Health Network (REACHnet), were extracted for all patients with T2D aged C 18 years who had encounter dates between January 2011 and August 2017 and C 1 HbA1c laboratory value(s) \ 90 days before BI initiation and C 2 HbA1c laboratory values within 1 year after BI initiation and who met the inclusion criteria for GLP-1 RA initiation set for Cohorts 1, 2, or 3. The primary endpoints were the proportion of patients achieving HbA1c \ 7.0%, which was estimated via Kaplan-Meier analysis, and change in HbA1c within 12 months. Results: Overall, 869 patients were analyzed, of whom 109 were in Cohort 1, 301 in Cohort 2, and 459 in Cohort 3. Baseline HbA1c was 10.3 ± 2.1, 10.3 ± 2.0, and 10.2 ± 2.1% for these three cohorts, respectively. Statistically significantly more patients in Cohort 1 than in Cohort 3 achieved HbA1c \ 7.0% (33.4 vs. 20.9%, respectively; p = 0.0186). Mean observed reductions in HbA1c at 12 months were-1.7% (Cohort 1),-1.5% (Cohort 2), and-1.3% (Cohort 3). Conclusions: Simultaneous initiation of BI and GLP-1 RA achieves glycemic control more effectively than sequential initiation of BI with GLP-1 RA added beyond 90 days.

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“…Even if the previously used oral antihyperglycemic drugs are still as important, newer drugs will in the future replace metformin and sulfonylurea. In this new era of 2018, we are focusing on new add-on oral hypoglycemic drugs which could possibly be adopted by the population of patients with T2DM [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Adverse Drug Events Associated with sitagliptin Versus canagliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus: A Systematic Comparison Through a Meta-Analysis

Bundhun

Huang

2018

Diabetes Ther

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IntroductionIn this meta-analysis, we aimed to systematically compare the adverse drug events associated with sitagliptin (100 mg) versus canagliflozin 100 or 300 mg in patients who were treated for type 2 diabetes mellitus (T2DM).MethodsOnline databases were searched for relevant studies comparing sitagliptin (100 mg) versus canagliflozin. Adverse drug events were considered as the clinical endpoints. The analysis was carried out by RevMan software whereby risk ratios (RR) and 95% confidence intervals (CI) were generated.ResultsFive studies with a total number of 2322 patients were included. When sitagliptin (100 mg) was compared with canagliflozin (100 mg), the endpoints of any adverse events, adverse events leading to drug discontinuation, serious adverse events, urinary tract infections, hypoglycemia, and adverse events related to hypovolemia were not significantly different: (RR 1.10, 95% CI 1.00–1.21; P = 0.05), (RR 1.20, 95% CI 0.67–2.16; P = 0.54), (RR 0.90, 95% CI 0.49–1.66; P = 0.73), (RR 1.26, 95% CI 0.77–2.08; P = 0.36), (RR 1.01, 95% CI 0.30–3.43; P = 0.99), and (RR 1.76, 95% CI 0.52–5.94; P = 0.36), respectively. However, canagliflozin was associated with increased genital mycotic infection (RR 4.32, 95% CI 2.11–8.83; P = 0.0001). When genital mycotic infections associated with sitagliptin versus canagliflozin were compared in male and female patients separately, the risk was still significantly higher with canagliflozin: (RR 7.00, 95% CI 2.44–20.06; P = 0.003) and (RR 4.02, 95% CI 2.22–7.27; P = 0.00001), respectively. The same results were obtained when sitagliptin (100 mg) was compared to canagliflozin 300 mg.ConclusionsCanagliflozin was associated with a significantly higher risk of genital mycotic infections when compared to sitagliptin. However, the other adverse drug events were similarly manifested when sitagliptin 100 mg was compared to either canagliflozin 100 or 300 mg.

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Newer oral and noninsulin therapies to treat type 2 diabetes mellitus

Cited by 5 publications

References 41 publications

Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

Impact of Simultaneous Versus Sequential Initiation of Basal Insulin and Glucagon-like Peptide-1 Receptor Agonists on HbA1c in Type 2 Diabetes: A Retrospective Observational Study

Adverse Drug Events Associated with sitagliptin Versus canagliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus: A Systematic Comparison Through a Meta-Analysis

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