Effect of Adding a Sulfonylurea in Patients with Non-Insulin-Dependent Diabetes Mellitus Previously Well Controlled with Insulin

For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

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“…[ 138 ] However, no change in body weight was observed by addition of SUs to insulin in several older RCTs. [ 146 147 ]…”

Section: S Ulfonylureas and C Ombinationmentioning

confidence: 99%

Consensus recommendations on sulfonylurea and sulfonylurea combinations in the management of Type 2 diabetes mellitus – International Task Force

Kalra

Bahendeka

Sahay

et al. 2018

Indian J Endocr Metab

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Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis

et al. 2013

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Aims/hypothesisSulfonylureas are widely prescribed glucose-lowering medications for diabetes, but the extent to which they improve glycaemia is poorly documented. This systematic review evaluates how sulfonylurea treatment affects glycaemic control.MethodsMedline, EMBASE, the Cochrane Library and clinical trials registries were searched to identify double-blinded randomised controlled trials of fixed-dose sulfonylurea monotherapy or sulfonylurea added on to other glucose-lowering treatments. The primary outcome assessed was change in HbA1c, and secondary outcomes were adverse events, insulin dose and change in body weight.ResultsThirty-one trials with a median duration of 16 weeks were included in the meta-analysis. Sulfonylurea monotherapy (nine trials) lowered HbA1c by 1.51% (17 mmol/mol) more than placebo (95% CI, 1.25, 1.78). Sulfonylureas added to oral diabetes treatment (four trials) lowered HbA1c by 1.62% (18 mmol/mol; 95% CI 1.0, 2.24) compared with the other treatment, and sulfonylurea added to insulin (17 trials) lowered HbA1c by 0.46% (6 mmol/mol; 95% CI 0.24, 0.69) and lowered insulin dose. Higher sulfonylurea doses did not reduce HbA1c more than lower doses. Sulfonylurea treatment resulted in more hypoglycaemic events (RR 2.41, 95% CI 1.41, 4.10) but did not significantly affect the number of other adverse events. Trial length, sulfonylurea type and duration of diabetes contributed to heterogeneity.Conclusions/interpretationSulfonylurea monotherapy lowered HbA1c level more than previously reported, and we found no evidence that increasing sulfonylurea doses resulted in lower HbA1c. HbA1c is a surrogate endpoint, and we were unable to examine long-term endpoints in these predominately short-term trials, but sulfonylureas appear to be associated with an increased risk of hypoglycaemic events.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-2856-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus

Lin

Cai

Yang

et al. 2020

BMC Med

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Background The placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine. Methods Literature research was conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies published between the date of inception and June 2019. Randomized placebo-controlled trials conducted in type 1and type 2 diabetes mellitus (T1DM/T2DM) were included. Random-effects model and meta-regression analysis were accordingly used. This meta-analysis was registered in PROSPERO as CRD42014009373. Results Significantly weight elevation (effect size (ES) = 0.33 kg, 95% CI, 0.03 to 0.61 kg) was observed in patients with placebo treatments in T1DM subgroup while significantly HbA1c reduction (ES = − 0.12%, 95% CI, − 0.16 to − 0.07%) and weight reduction (ES = − 0.40 kg, 95% CI, − 0.50 to − 0.29 kg) were observed in patients with placebo treatments in T2DM subgroup. Greater HbA1c reduction was observed in patients with injectable placebo treatments (ES = − 0.22%, 95% CI, − 0.32 to − 0.11%) versus oral types (ES = − 0.09%, 95% CI, − 0.14 to − 0.04%) in T2DM (P = 0.03). Older age (β = − 0.01, 95% CI, − 0.02 to − 0.01, P < 0.01) and longer diabetes duration (β = − 0.02, 95% CI, − 0.03 to − 0.21 × 10−2, P = 0.03) was significantly associated with more HbA1c reduction by placebo in T1DM. However, younger age (β = 0.02, 95% CI, 0.01 to 0.03, P = 0.01), lower male percentage (β = 0.01, 95% CI, 0.22 × 10−2, 0.01, P < 0.01), higher baseline BMI (β = − 0.02, 95% CI, − 0.04 to − 0.26 × 10−2, P = 0.02), and higher baseline HbA1c (β = − 0.09, 95% CI, − 0.16 to − 0.01, P = 0.02) were significantly associated with more HbA1c reduction by placebo in T2DM. Shorter diabetes duration (β = 0.06, 95% CI, 0.06 to 0.10, P < 0.01) was significantly associated with more weight reduction by placebo in T2DM. However, the associations between baseline BMI, baseline HbA1c, and placebo response were insignificant after the adjusted analyses. Conclusion The placebo response in diabetes mellitus was systematically outlined. Age, sex, disease severity (indirectly reflected by baseline BMI and baseline HbA1c), and disease duration were associated with placebo response in diabetes mellitus. The association between baseline BMI, baseline HbA1c, and placebo response may be the result of regression to the mean.

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Effect of Adding a Sulfonylurea in Patients with Non-Insulin-Dependent Diabetes Mellitus Previously Well Controlled with Insulin

Cited by 7 publications

References 19 publications

Consensus recommendations on sulfonylurea and sulfonylurea combinations in the management of Type 2 diabetes mellitus – International Task Force

Consensus recommendations on sulfonylurea and sulfonylurea combinations in the management of Type 2 diabetes mellitus – International Task Force

Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis

Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus

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