Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes

Zhou, Yue; Geng, Zhuang; Wang, Xiang; Huang, Yajing; Wang, Yangang

doi:10.1002/dmrr.3223

Cited by 20 publications

(32 citation statements)

References 35 publications

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“…Canagliflozin and other SGLT2 inhibitors have been shown to reduce hospitalizations for HF and renal events 2‐5 in patients with T2DM and recently also in patients without T2DM 5,28 . Canagliflozin was shown to reduce cardiovascular and renal events, including hospitalizations for HF, even in patients with chronic kidney disease and albuminuria, 29 further supporting its role in patients with T2DM to reduce cardiovascular events.…”

Section: Discussionmentioning

confidence: 93%

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA‐HF study

Carbone

Billingsley

Canada

et al. 2020

Diabetes Metabolism Res

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Background Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. Methods We conducted a double‐blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) slope (co‐primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2, ventilatory anaerobic threshold (VAT), cardiac function and quality of life (ie, Minnesota Living with Heart Failure Questionnaire [MLHFQ]), at baseline and 12‐week follow‐up. Results The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 and VE/VCO2 slope between the two groups (P = .083 and P = .98, respectively). Canagliflozin improved lean peak VO2 (+2.4 mL kgLM−1 min−1, P = .036), VAT (+1.5 mL kg−1 min−1, P = .012) and VO2 matched for respiratory exchange ratio (+2.4 mL Kg−1 min−1, P = .002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (−12.1, P = .018). Conclusions In this small and short‐term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO2, VAT and quality of life.

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Section: Discussionmentioning

confidence: 93%

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA‐HF study

Carbone

Billingsley

Canada

et al. 2020

Diabetes Metabolism Res

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“…This finding has important implications in the routine care of T2D because DPP‐4i have become popular second‐line GLM worldwide and in Italy, 35 despite they are devoid of solid cardio‐renal protective effects 36 . We recognize that combination therapy with SGLT2i and DPP‐4i or incretin‐based therapies in general, which has recently become available in many countries, can provide an additional benefit on several clinical outcomes 37 …”

Section: Discussionmentioning

confidence: 99%

Comparative effectiveness of dapagliflozin vs DPP‐4 inhibitors on a composite endpoint of HbA1c, body weight and blood pressure reduction in the real world

Morieri

Consoli

Sesti

et al. 2020

Diabetes Metabolism Res

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BackgroundTreatment of type 2 diabetes (T2D) should aim at preventing or delaying complications through the control of glycaemia and cardiovascular risk factors. We herein compared the SGLT‐2 inhibitor dapagliflozin vs DPP‐4 inhibitors (DPP‐4i) on a composite endpoint of glycaemic and extraglycaemic effectiveness.MethodsThis was a multicentre, retrospective real‐world study conducted at 56 outpatient clinics in Italy. We collected data on patients newly started on dapagliflozin or DPP‐4i in 2015‐2017. The primary endpoint was the proportion of patients attaining a simultaneous reduction of HbA1c ≥0.5%, body weight ≥2 kg, systolic blood pressure (SBP) ≥2 mmHg. Confounding by indication was addressed by propensity score matching (PSM) or multivariable adjustment (MVA).ResultsPatients initiating dapagliflozin (n = 2091) or DPP‐4i (n = 2144) differed for most clinical characteristics. After PSM, two well‐balanced groups of 1149 patients each were compared. The primary endpoint was reached in a greater proportion of patients who received dapagliflozin (17.6%) compared to DPP‐4i (11.7%), with a relative risk of 1.50 (1.21‐1.86; P < .001). Similar results were obtained in the as‐treated and intention‐to‐treat datasets or using MVA in place of PSM. The beneficial effect of dapagliflozin was mainly due to its greater effectiveness on body weight and, to a lesser extent, on SBP. The change in HbA1c did not differ between groups.ConclusionsT2D patients initiating the SGLT2i dapagliflozin had a greater probability of attaining a composite endpoint of clinically relevant reductions in HbA1c, body weight and SBP, compared to similar patients initiating a DPP‐4i in the same period and healthcare setting.

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“…39 Notably, based on data from the DURATION-8 trial, which reported both short-term and long-term results, the overall body SGLT2i has been addressed in four previous meta-analyses. [7][8][9][10] However, these meta-analyses only synthesized data from comparisons with an SGLT2i. Instead, we also analysed studies and study arms that included a GLP-1RA as a comparator.…”

Section: Mortality and Cardiovascular Outcomesmentioning

confidence: 99%

“…[7][8][9][10] However, either they focused solely on comparisons with SGLT2is and not with GLP-1RAs and did not incorporate data from all relevant randomized controlled trials (RCTs) published to date, or they did not take into consideration the pattern of combination therapy in each trial (sequential administration or co-initiation) in their analysis. [7][8][9][10] Sequential administration aims to improve patient adherence and minimize adverse events, while co-initiation therapy can lead to earlier achievement of therapeutic goals by targeting multiple pathogenic mechanisms simultaneously, as shown in the VERIFY (Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes) study. 11,12 We aimed to systematically retrieve, critically appraise and synthesize all currently available evidence evaluating the efficacy and safety of combination therapy with a GLP-1RA and an SGLT2i in patients with type 2 diabetes, by means of an up-to-date systematic review and meta-analysis of RCTs.…”

Section: Introductionmentioning

confidence: 99%

Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta‐analysis

Mantsiou

Karagiannis

Kakotrichi

et al. 2020

Diabetes Obesity Metabolism

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Aim To assess the efficacy and safety of combination therapy with a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) and a sodium‐glucose co‐transporter‐2 inhibitor (SGLT2i) in patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library and grey literature sources up to 2 December 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP‐1RA and SGLT2i, either as co‐initiation therapy or as add‐on to each other, against placebo or an active comparator. The primary outcome was change in HbA1c. Secondary outcomes included change in body weight, blood pressure and estimated glomerular filtration rate, and incidence of severe hypoglycaemia, all‐cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta‐analyses. Results Seven trials (1913 patients) were eligible. Compared with GLP‐1RA, GLP‐1RA/SGLT2i combination therapy was associated with a greater reduction in HbA1c (weighted mean difference −0.61%, 95% CI −1.09% to −0.14%, four studies), body weight (−2.59 kg, −3.68 to −1.51 kg, three studies) and systolic blood pressure (−4.13 mmHg, −7.28 to −0.99 mmHg, four studies). Compared with SGLT2i, GLP‐1RA/SGLT2i combination therapy reduced HbA1c (−0.85%, −1.19% to −0.52%, six studies) and systolic blood pressure (−2.66 mmHg, −5.26 to −0.06 mmHg, six studies), but not body weight (−1.46 kg, −2.94 to 0.03 kg, five studies). After excluding data for one trial that had a considerably longer duration than the remaining studies, body weight was also reduced versus SGLT2i (−1.79 kg, −2.99 to −0.59 kg, five studies). Combination therapy did not increase the incidence of severe hypoglycaemia. Data for mortality and cardiovascular outcomes were scarce. Conclusions GLP‐1RA/SGLT2i combination therapy seems to reduce HbA1c, body weight and systolic blood pressure without increasing the risk of severe hypoglycaemia compared with either GLP‐1RA or SGLT2i. No conclusions can be made regarding long‐term effectiveness or the effect on cardiovascular outcomes.

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Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes

Cited by 20 publications

References 35 publications

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA‐HF study

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA‐HF study

Comparative effectiveness of dapagliflozin vs DPP‐4 inhibitors on a composite endpoint of HbA1c, body weight and blood pressure reduction in the real world

Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta‐analysis

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