Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis

Qian, Dehui; Zhang, Tiantian; Tan, Xiaohong; Zheng, Peiying; Liang, Zhuoru; Xie, Jingmei; Jiang, Jie; Situ, Bing

doi:10.1371/journal.pone.0202563

Cited by 14 publications

(10 citation statements)

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“…A recent network meta-analysis of different AHA classes added to SU monotherapy concluded that SGLT2 inhibitors have distinct advantages over other AHA classes, as they not only significantly improve glycemic control but they may also reduce the risk of hypoglycemia and BW [39]. In both the primary and post-hoc analyses of the VERTIS CV substudy reported here, the mean reductions in BW from baseline with both doses of ertugliflozin were commensurate with the reduction predicted in that meta-analysis.…”

Section: Discussionsupporting

confidence: 73%

Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV

et al. 2021

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Introduction Sulfonylureas (SU) are commonly used antihyperglycemic agents. VERTIS CV was the cardiovascular outcome study for the sodium-glucose cotransporter 2 inhibitor ertugliflozin. Enrollment of patients in VERTIS CV occurred in two sequential cohorts (Cohort 1 and Cohort 2). Methods This substudy assessed the efficacy and safety of adding ertugliflozin to SU monotherapy. The primary endpoint was the change in HbA1c from baseline at 18 weeks. Results Among the 8246 patients who were randomized in VERTIS CV, 157 patients in Cohort 1 and 135 patients in Cohort 2 were on SU monotherapy at baseline. In the prespecified analysis (Cohort 1 only), the least squares (LS) mean HbA1c change from baseline for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was − 0.56%, − 0.91%, and − 0.78%, respectively (placebo-adjusted LS mean [95% CI] change: − 0.35% [− 0.72%, 0.02%]; − 0.22% [− 0.60%, 0.16%] for ertugliflozin 5 and 15 mg, respectively; p > 0.05 for both). In a post-hoc analysis that included Cohorts 1 and 2 ( N = 292), the LS mean HbA1c change from baseline at week 18 for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was − 0.31%, − 0.77%, and − 0.68%, respectively (placebo-adjusted change: − 0.46% [− 0.73%, − 0.18%]; − 0.37% [− 0.66%, − 0.09%]; p = 0.001 and 0.01 for ertugliflozin 5 and 15 mg, respectively). In Cohort 1, adverse events were reported in 45.8%, 47.3%, and 25.9% of patients with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg. The incidence rates of symptomatic hypoglycemia were 0.0%, 5.5%, and 3.7%, respectively, with no cases of severe hypoglycemia. The safety profile was similar for Cohorts 1 and 2 combined. Conclusion The addition of ertugliflozin to SU monotherapy reduced HbA1c but did not result in significant placebo-adjusted reductions from baseline according to the prespecified primary analysis ( n = 157); however, in a post-hoc analysis with a larger patient population ( n = 292), significant and clinically relevant HbA1c reductions were observed. Ertugliflozin was generally well tolerated. Trial Registration ClinicalTrials.gov identifier: NCT01986881. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01018-w.

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Section: Discussionsupporting

confidence: 73%

Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV

et al. 2021

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“…Our results were consistent with those of a meta-analysis in which the use of metformin increased the risk of hypoglycemia, resulting in a 1.5-times higher risk in the SU and metformin group than in the SU monotherapy group. 40 The risk of hypoglycemia was 1.6-fold higher in the group receiving combination therapy of SUs, DPP-4i, and metformin than in the SUs and DPP-4i groups. These results are probably due to the combined effect of increase in insulin sensitivity by metformin and stimulation of insulin secretion by SUs, because metformin alone does not increase the risk of hypoglycemia significantly.…”

Section: Discussionmentioning

confidence: 92%

“…41 A meta-analysis also showed that the combination of SUs and metformin resulted in a 2.0-fold higher risk of hypoglycemia than SUs and DPP-4i. 40 Chloramphenicol, isoniazid, linezolid, and prothionamide showed a grouped aOR of 5.48 (95% CI 2.19-13.68). However, the sample size was small, and further studies are needed.…”

Section: Discussionmentioning

confidence: 94%

Effects of Co‐administration of Sulfonylureas and Antimicrobial Drugs on Hypoglycemia in Patients with Type 2 Diabetes Using a Case‐Crossover Design

et al. 2020

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Objectives The purpose of this study was to investigate the effect of sulfonylureas (SUs) and antimicrobial co‐administration on hypoglycemia in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a case‐crossover study using the Korean Health Insurance Review and Assessment Service‐National Inpatient Sample database, using data from 2014 to 2016. Hospitalized adult patients with T2DM who were diagnosed with hypoglycemia and prescribed SUs for at least 120 days were included. Different risk ratings of severity of drug–drug interactions were considered, including “level X, D, or C” in Lexi‐Interact online and “contraindicated, major, or moderate” in Micromedex. Exposure to antimicrobials in the 30‐day period before the first hypoglycemia diagnosis was assessed. Two control periods (61–90 and 91–120 days) were matched before the diagnosis date. Conditional logistic regression analysis was conducted to compare the odds of antimicrobial exposure. Results A total of 9339 patients were included. The mean age of the patients was 71.3 ± 10.6 years, and 4818 (51.6%) were women. An increased risk of hypoglycemia was associated with co‐administration of SUs and certain antimicrobials (adjusted odds ratio [aOR] 2.56, 95% confidence interval [CI] 2.34–2.80). The antimicrobial agents that were associated with an increased risk of hypoglycemia, when co‐administered with SUs, were sulfonamides (aOR 2.99, 95% CI 1.99–4.52), fluoroquinolones (aOR 2.62, 95% CI 2.38–2.89), macrolides (aOR 2.48, 95% CI 1.88–3.27), and tetracyclines (aOR 1.56, 95% CI 1.05–2.33). Conclusions Co‐administration with SUs and certain antimicrobials increased the risk of hypoglycemia. Thus, clinically relevant interactions in patients concurrently using SUs and antimicrobials should be monitored, especially within 30 days after co‐administration.

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“…We had expected weight to be an important discriminating factor in the choice of anti-diabetes treatment as it significantly influences glycemic control and macrovascular complications. It is also well known that overweight and obese patients are more likely to be affected by T2DM, with the odds ratio increasing from the lowest BMI category to the highest [ 1 , 4 , 16 – 19 ].…”

Section: Discussionmentioning

confidence: 99%

Prescription of Sulphonylureas among Patients with Type 2 Diabetes Mellitus in Italy: Results from the Retrospective, Observational Multicentre Cross-Sectional SUSCIPE (Sulphonyl_UreaS_Correct_Internal_Prescription_Evaluation) Study

et al. 2020

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Introduction: Recent guidelines for the treatment of type 2 diabetes mellitus (T2DM) provide evidence supporting limited use of sulphonylureas (SUs), especially in specific risk patient categories, yet data from national registries still suggest their widespread use. The aim of this study was to investigate characteristics of patients with diabetes treated with SUs and quantify the proportion of patients that met the Digital Features To view digital features for this article go to

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Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis

Cited by 14 publications

References 57 publications

Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV

Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV

Effects of Co‐administration of Sulfonylureas and Antimicrobial Drugs on Hypoglycemia in Patients with Type 2 Diabetes Using a Case‐Crossover Design

Prescription of Sulphonylureas among Patients with Type 2 Diabetes Mellitus in Italy: Results from the Retrospective, Observational Multicentre Cross-Sectional SUSCIPE (Sulphonyl_UreaS_Correct_Internal_Prescription_Evaluation) Study

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