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Effect of ertugliflozin on glycemic levels, blood pressure and body weight of patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

ABSTRACT:

Purpose

To conduct a meta-analysis to evaluate the effect of ertugliflozin on long-term hemoglobin A1c (HbA1c), body weight and blood pressure (BP).

Methods

Online databases available were searched from their inception to February 2020. Randomized controlled trials (RCTs) comparing ertugliflozin to either placebo or an active control drug were included. Data on four efficacy outcomes were extracted, namely: HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP) and body weight. Continuous outcomes were pooled using a random-effects model and presented as weighted mean differences (WMDs) and corresponding 95% CIs. Additionally, a subgroup analysis was done to compare two doses of ertugliflozin (5 mg and 15 mg). A sensitivity analysis was also performed by eliminating studies using active drugs as controls.

Results

From a total of 123 search results, eight studies were included. Compared to the control group, ertugliflozin was associated with a significant decrease in SBP (WMD: -3.64 mmHg, 95% CI [-4.39,-2.90]; p < 0.001; I² = 0%) and DBP (WMD: -1.13 mmHg, 95% CI [-1.67,-0.60], p < 0.001; I² = 0%). Similarly, significant reductions in body weight (WMD: -2.35 kg, 95% CI [-2.94,-1.77]; p < 0.001; I² = 0%) as well as HbA1c (WMD: -0.41%, 95% CI [-0.62,-0.20]; p < 0.001; I² = 0%) were seen with ertugliflozin. Subgroup analysis demonstrated no significant difference in efficacy between the two doses in any of the four outcomes.

Conclusion

Ertugliflozin results in significant reductions in HbA1c, body weight, SBP and DBP, when compared to control. Subgroup analyses suggest that these effects are not dose-dependent.

SUBMITTER: Zaman M

PROVIDER: S-EPMC7843749 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels. DESIGN:Systematic review and meta-analyses of randomised controlled trials. DATA SOURCES:CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, we contacted researchers, pharmaceutical companies, and authorities. ELIGIBILITY CRITERIA:Randomised controlled trials including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets. RESULTS:49 trials, including 73,738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Metaregression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure. CONCLUSIONS:Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.

Project description:BackgroundThe efficacy of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, for glycemic and blood pressure (BP) control has been demonstrated in phase 3 studies. To further evaluate the effects of ertugliflozin on BP and other hemodynamic parameters, an analysis was conducted on the pooled patient populations from these studies.MethodsThis was a post hoc analysis of data from three phase 3 studies (NCT01958671, NCT02033889, and NCT02036515) of adults with type 2 diabetes mellitus who received placebo, ertugliflozin 5 mg, or ertugliflozin 15 mg. Outcomes at 26 weeks were analyzed for the pooled population and according to relevant baseline factors, including BP.ResultsOf the 1544 patients included (placebo, n = 515; ertugliflozin 5 mg, n = 519; ertugliflozin 15 mg, n = 510), most (67.4-69.0%) had hypertension at baseline. Mean baseline BP was similar across treatment groups (placebo, 129.7/78.0 mmHg; ertugliflozin 5 mg, 131.0/78.4 mmHg; ertugliflozin 15 mg, 130.5/78.4 mmHg). At Week 26, placebo-adjusted least squares (LS) mean changes (95% confidence intervals [CI]) from baseline in systolic BP (SBP) were - 3.7 mmHg (- 5.1, - 2.3) for both ertugliflozin doses. Reductions were consistent across all baseline subgroups. At Week 26, more patients with a baseline SBP ≥ 130 mmHg had a SBP < 130 mmHg with ertugliflozin (38.7% both doses) than with placebo (24.0%), and more patients with a baseline SBP ≥ 140 mmHg attained a SBP < 140 mmHg with ertugliflozin (59.5% [5 mg] and 66.7% [15 mg]) than with placebo (43.8%). Placebo-adjusted LS mean changes (95% CI) in diastolic BP (DBP) with ertugliflozin 5 mg and 15 mg were - 1.8 mmHg (- 2.7, - 0.9) and - 1.6 mmHg (- 2.5, - 0.7), respectively, and in pulse rate were - 1.3 beats per minute (bpm) (- 2.2, - 0.3) and - 1.5 bpm (- 2.5, - 0.6), respectively. Greater reductions in pulse pressure, mean arterial pressure, and double product were observed with ertugliflozin than with placebo. Incidence of adverse event-related osmotic diuresis was low, but greater with ertugliflozin (2.9% [5 mg], 2.4% [15 mg]) than placebo (1.0%).ConclusionErtugliflozin treatment led to reductions in SBP, DBP, and pulse rate relative to placebo. Reductions in SBP were generally consistent across the subgroups evaluated. Trial registration NCT01958671; NCT02033889; NCT02036515.