scholarly journals Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

AbstractDiabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = − 0.10%, 95% CI [− 0.17, − 0.03], body weight (MD = − 4.57 kg, 95% CI [− 4.74, − 4.39], systolic blood pressure (MD = − 4.77 mmHg, 95% CI [− 5.39, − 4.16]), diastolic blood pressure (MD = − 2.07 mmHg, 95% CI [− 2.74, − 1.40], and fasting plasma glucose (MD = − 0.55 mmol/L, 95% CI [− 0.69, − 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

scholarly journals Cardiovascular safety and efficacy of combination therapy with metformin and sodium-glucose cotransporter-2 inhibitors versus metformin and sulfonylureas in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

AbstractBackgroundDiabetes mellitus is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin and sodium-glucose cotransporter-2 inhibitors versus metformin and sulfonylureas in patients with type 2 diabetes.MethodWe searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 and without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin- sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycosylated hemoglobin A1C, body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Random effect model was carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between the two combination therapies.ResultsOf 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significance difference in all-cause mortality (RR = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR=0.96, 95% CI [0.79, 1.17]) and adverse events (RR=1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR= 0.13, 95% CI [0.10, 0.17], P<0.00001). Participants taking metformin-sodium-glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (MD= −0.10, 95% CI [−0.17, −0.03] %, body weight (MD= −4.57, 95% CI [−4.74, −4.39] kg, systolic blood pressure (MD=-4.77, 95% CI [−5.39, −4.16] mmHg, p<0.00001), diastolic blood pressure (MD=-2.07, 95% CI [−2.74, −1.40] mmHg, and fasting plasma glucose (MD= −0.55, 95% CI [−0.69, −0.41] mmol/L, p < 0.00001).ConclusionA combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

scholarly journals Efficacy and Safety of a Sodium-Glucose Co-Transporter-2 Inhibitor Versus Placebo as an Add-on Therapy for People With Type 2 Diabetes Inadequately Treated With Metformin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A469-A470
Author(s):  
Jia Leng Lim ◽  
Georgina Bergero ◽  
Yogesh Acharya ◽  
James Shaw ◽  
Aaron Liew
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Mycotic Infections

Abstract Metformin monotherapy is often insufficient to achieve or sustain glycemic targets in people with type 2 diabetes. Therefore, we performed a systematic review and meta-analysis to assess the efficacy, safety and tolerability of sodium-glucose co-transporter-2 inhibitors versus placebo as add-on therapy after metformin in type 2 diabetes. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search was performed in the PubMed, www.clinicaltrials.gov and Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials up until 30th October 2020 that compared sodium-glucose co-transporter-2 inhibitors versus placebo as add-on therapy to metformin. A random-effects model was used. Thirteen randomized controlled trials (4270 participants) met the inclusion criteria. Compared with placebo, sodium-glucose co-transporter-2 inhibitor treatment, as add-on therapy to metformin, was associated with a significant reduction in HbA1c level (mean difference [MD]: -0.6%, 95% CI: -0.7, -0.5; p&lt;0.01), fasting plasma glucose level (MD: -1.4mmol/l; 95% CI; -1.5, -1.3; p&lt;0.01), weight (MD: -2.0kg; 95% CI: -2.2, -1.8; p&lt;0.01), systolic blood pressure (MD: -4.7mmHg; 95% Cl: -5.4, -3.9; p&lt;0.01) and diastolic blood pressure (MD: -2.0mmHg; 95% Cl: -2.5, -1.5; p&lt;0.01). Significantly more participants achieved HbA1c &lt;7% (odds ratio [OR]: 3.1; 95% CI: 2.6, 3.6; p&lt;0.01) in the sodium-glucose co-transporter-2 inhibitor group. Genital mycotic infections (OR: 2.6; 95% CI: 1.4, 4.6; p&lt;0.01) were more common with sodium-glucose co-transporter-2 inhibitors, but there was no significant statistical difference in urinary tract infections (OR: 1.4; 95% CI: 1.0, 2.0; p=0.06), in hypoglycemia (OR: 1.5; 95% CI: 1.0, 2.4; p=0.07), or in discontinuation rates due to adverse events (OR: 0.9; 95% CI: 0.6, 1.5; p=0.68) between the two groups. In summary, in comparison with placebo, add-on therapy with a sodium-glucose co-transporter-2 inhibitor is significantly more efficacious in lowering HbA1c, fasting plasma glucose, weight and blood pressure in people with type 2 diabetes following inadequate glycemic control with metformin. The rate of discontinuation due to adverse events was similar despite higher risk of genital mycotic infections.

scholarly journals Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Conventional Therapy at Different Periods: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jing Huang ◽  
Shuyuan Xiong ◽  
Shenglan Ding ◽  
Qingfeng Cheng ◽  
Zhiping Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adverse Events ◽  
Conventional Therapy ◽  
Meta Analysis ◽  
Control Group ◽  
Controlled Trials ◽  
Randomized Controlled

Aims. To assess the safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with conventional therapy at different periods. Methods. We searched PubMed, Embase, and The Cochrane Library from inception to September 23, 2020. A total of six studies involving 4120 patients were included. Results. Compared with the control group, 15 mg and 5 mg of ertugliflozin were associated with higher risks of genital mycotic infections (GMIs) at 26 weeks ( p < 0.0001 and p < 0.0001 , respectively), 52 weeks ( p < 0.00001 and p < 0.0001 , respectively), and 104 weeks ( p < 0.00001 and p < 0.0001 , respectively). Moreover, females had a higher risk of GMIs than males in the 15 mg group at 26 weeks ( p = 0.0008 ), 52 weeks ( p < 0.0001 ), and 104 weeks ( p = 0.02 ). At 104 weeks, 15 mg and 5 mg of ertugliflozin showed beneficial effects on symptomatic hypoglycemia ( p < 0.00001 and p = 0.004 , respectively) compared with the effects observed in the control group. Compared with the control group, 15 mg and 5 mg of ertugliflozin were associated with higher risks of drug-related adverse events at 26 weeks ( p = 0.002 and p = 0.002 , respectively); 15 mg of ertugliflozin was associated with a higher risk of discontinuation related to adverse events at 104 weeks ( p = 0.03 ). No significant differences were found in the remaining safety outcomes. Conclusion. This meta-analysis of randomized controlled trials indicates that ertugliflozin is tolerated by T2DM, but the risk of GMIs is noteworthy, especially among females in the high-dose group.

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