Efficacy and safety of sotagliflozin in patients with type <scp>2</scp> diabetes and severe renal impairment

Cherney, David Z.I.; Ferrannini, Ele; Umpiérrez, Guillermo E.; Rosenstock, Julio; Carroll, Amy K.; Lapuerta, Pablo; Banks, Phillip; Agarwal, Rajiv

doi:10.1111/dom.14513

Cited by 44 publications

(61 citation statements)

References 34 publications

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“…The safety of sotagliflozin in patients with type 2 diabetes and renal impairment was also established in a recently published phase 3 trial, in which 277 patients with stage 4 chronic kidney disease were randomly assigned to sotaglifliozin or placebo. Overall, after 52 weeks, treatment with sotagliflozin resulted in sustained glycaemic control and an overall safe profile 17 …”

Section: Discussionmentioning

confidence: 93%

“…The flow diagram of the study selection process is depicted in Figure S1. Eleven trials comprising 16 411 subjects were included in our systematic review and meta‐analysis 7,8,15‐23 . Study and participants’ baseline characteristics are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Eleven trials comprising 16 411 subjects were included in our systematic review and meta-analysis. 7,8,[15][16][17][18][19][20][21][22][23] Study and participants' baseline characteristics are summarized in Table 1. Four studies were identified as full-text reports published in medical journals, while the remaining studies were identified as trial reports published in international clinical trial registries.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…The favourable effect of sotagliflozin against placebo was consistent regardless of trial duration (WMD À0.48%, 95% CI À0.72 to À0.25, I 2 = 84%, five studies with a duration of less than 52 weeks; and À0.35%, À0.53 to À0.17, I 2 = 32%, four studies with a duration of at least 52 weeks, P value for subgroup interaction .39). Finally, in a post hoc analysis excluding trials that exclusively enrolled patients with cardiovascular or renal disease, 7,16,17 treatment with sotagliflozin consistently reduced HbA1c levels compared with placebo, while heterogeneity was substantially reduced (WMD À0.53%, 95% CI À0.69 to À0.38, I 2 = 43%, six studies).…”

Section: Glycaemic Efficacymentioning

confidence: 99%

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Sotagliflozin for patients with type 2 diabetes: A systematic review and meta‐analysis

Avgerinos

Karagiannis

Kakotrichi

et al. 2021

Diabetes Obesity Metabolism

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Aim: To assess the efficacy and safety of sotagliflozin in patients with type 2 diabetes.Methods: We searched Medline, Embase, the Cochrane Library, and grey literature sources up to August 2021 for randomized controlled trials (RCTs) that compared sotagliflozin with placebo or other antidiabetic agents in patients with type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed three secondary efficacy and 15 safety outcomes. We synthesized data using weighted mean differences (WMDs) and odds ratios (ORs), along with 95% confidence intervals (CIs).Results: We included 11 RCTs comprising 16 411 subjects in the meta-analysis. Compared with placebo, sotagliflozin reduced HbA1c (WMD À0.42%, 95% CI À0.56 to À0.29), body weight (WMD À1.33 kg, 95% CI À1.57 to À1.09), and systolic blood pressure (WMD À2.44 mmHg, 95% CI À2.81 to À2.07). No difference was evident against other active comparators. Sotagliflozin reduced myocardial infarction (OR 0.72, 95% CI 0.54 to 0.97) and heart failure (OR 0.68, 95% CI 0.58 to 0.79) compared with placebo, and had a neutral effect on all-cause mortality, cardiovascular mortality, and stroke.Treatment with sotagliflozin was safe regarding the incidence of serious adverse events, hypoglycaemia, and diabetic ketoacidosis. Nevertheless, it was associated with an increased incidence of diarrhoea, genital infections, and volume depletion events.Conclusions: Sotagliflozin reduces blood glucose, body weight, and systolic blood pressure, and demonstrates a beneficial effect on heart failure and myocardial infarction. Its overall safety profile is comparable with other sodium-glucose cotransporter-2 inhibitors.

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Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Glycaemic Efficacymentioning

confidence: 99%

See 2 more Smart Citations

Sotagliflozin for patients with type 2 diabetes: A systematic review and meta‐analysis

Avgerinos

Karagiannis

Kakotrichi

et al. 2021

Diabetes Obesity Metabolism

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“…Previously, 277 patients with stage 4 CKD were included in the study. The results demonstrated that the sotagliflozin group had fewer adverse cardiovascular events than in the placebo group [ 30 ]. Our study indicated that patients with stage 3a or 3b CKD had a much lower risk of adverse cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

Zhou

Zheng

et al. 2022

PLoS ONE

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Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

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Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

Mc Causland,

Claggett,

Vaduganathan

et al. 2024

JAMA Cardiol

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ImportanceAn initial decline in estimated glomerular filtration rate (eGFR) is expected after initiating a sodium-glucose cotransporter-2 inhibitor (SGLT2i) and has been observed across patients with diabetes, chronic kidney disease, and heart failure.ObjectiveTo examine the implications of initial changes in eGFR among patients with heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial.Design, Setting, and ParticipantsThis was a prespecified analysis of the results of the DELIVER randomized clinical trial, which was an international multicenter study of patients with EF greater than 40% and eGFR greater than or equal to 25. The DELIVER trial took place from August 2018 to March 2022. Data for the current prespecified study were analyzed from February to October 2023.InterventionDapagliflozin, 10 mg per day, or placebo.Main Outcomes and MeasuresIn this prespecified analysis, the frequency of an initial eGFR decline (baseline to month 1) was compared between dapagliflozin and placebo. Cox models adjusted for baseline eGFR and established prognostic factors were fit to estimate the association of an initial eGFR decline with cardiovascular (cardiovascular death or heart failure event) and kidney (≥50% eGFR decline, eGFR&lt;15 or dialysis, death from kidney causes) outcomes, landmarked at month 1, stratified by diabetes.ResultsStudy data from 5788 participants (mean [SD] age, 72 [10] years; 3253 male [56%]) were analyzed. The median (IQR) change in eGFR level from baseline to month 1 was −1 (−6 to 5) with placebo and −4 (−9 to 1) with dapagliflozin (difference, −3; P &lt; .001). A higher proportion of patients assigned to dapagliflozin developed an initial eGFR decline greater than 10% vs placebo (1144 of 2892 [40%] vs 737 of 2896 [25%]; odds ratio, 1.9; 95% CI, 1.7-2.1; P difference &lt;.001). An initial eGFR decline of greater than 10% (vs ≤10%) was associated with a higher risk of the primary cardiovascular outcome among those randomized to placebo (adjusted hazard ratio [aHR], 1.33; 95% CI, 1.10-1.62) but not among those randomized to dapagliflozin (aHR, 0.90; 95% CI, 0.74-1.09; P for interaction = .01). Similar associations were observed when alternative thresholds of initial eGFR decline were considered and when analyzed as a continuous measure. An initial eGFR decline of greater than 10% was not associated with adverse subsequent kidney composite outcomes in dapagliflozin-treated patients (aHR, 0.94; 95% CI, 0.49-1.82).Conclusions and RelevanceAmong patients with HFmrEF or HFpEF treated with dapagliflozin, an initial eGFR decline was frequent but not associated with subsequent risk of cardiovascular or kidney events. These data reinforce clinical guidance that SGLT2is should not be interrupted or discontinued in response to an initial eGFR decline.Trial RegistrationClinicalTrials.gov Identifier: NCT03619213

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Efficacy and safety of sotagliflozin in patients with type 2 diabetes and severe renal impairment

Cited by 44 publications

References 34 publications

Sotagliflozin for patients with type 2 diabetes: A systematic review and meta‐analysis

Sotagliflozin for patients with type 2 diabetes: A systematic review and meta‐analysis

Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

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