Comparative efficacy of glucose‐lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta‐analysis

Τσάπας, Απόστολος; Karagiannis, Thomas; Kakotrichi, Panagiota; Avgerinos, Ioannis; Mantsiou, Chrysanthi; Tousinas, Georgios; Manolopoulos, Apostolos; Liakos, Aris; Malandris, Konstantinos; Matthews, David R.

doi:10.1111/dom.14451

Cited by 103 publications

(80 citation statements)

References 33 publications

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“…Previous clinical studies have shown that the SGLT2i treatment decreases systemic BP [14,15]. However, there were no significant changes in systemic BP, IOP, or OPP in either untreated or SGLT2i-treated mice during the follow-up period in the current study (Figure 1).…”

Section: Discussioncontrasting

confidence: 53%

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice

Hanaguri

Yokota

Kushiyama

et al. 2022

IJMS

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We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.

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Section: Discussioncontrasting

confidence: 53%

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice

Hanaguri

Yokota

Kushiyama

et al. 2022

IJMS

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“…We found that tirzepatide is superior in reducing HbA 1c compared with other injectable therapies, in particular basal insulin and once-weekly GLP-1 RAs. In addition, tirzepatide, even at the lowest maintenance dose of 5 mg, can reduce body weight to a greater extent compared with GLP-1 RAs including subcutaneous semaglutide which, in turn, has been shown to be superior to other glucose-lowering agents [ 28 ]. Notably, head-to-head data for tirzepatide vs GLP1 RAs are available only for dulaglutide 1.5 mg and semaglutide 1 mg. Higher doses of dulaglutide (3.0 mg and 4.5 mg) [ 29 ] have also received marketing approval for treatment of type 2 diabetes, while application for a label extension of semaglutide at the dose of 2.0 mg [ 30 ] has been submitted to the US FDA and has recently received a positive recommendation by the EMA.…”

Section: Discussionmentioning

confidence: 99%

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis

et al. 2022

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Aims/hypothesis Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes. Methods We searched PubMed, Embase, Cochrane and ClinicalTrials.gov up until 27 October 2021 for randomised controlled trials with a duration of at least 12 weeks that compared once-weekly tirzepatide 5, 10 or 15 mg with placebo or other glucose-lowering drugs in adults with type 2 diabetes irrespective of their background glucose-lowering treatment. The primary outcome was change in HbA1c from baseline. Secondary efficacy outcomes included change in body weight, proportion of individuals reaching the HbA1c target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%), and proportion of individuals with body weight loss of at least 5%, 10% or 15%. Safety outcomes included hypoglycaemia, gastrointestinal adverse events, treatment discontinuation due to adverse events, serious adverse events, and mortality. We used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess risk of bias for the primary outcome. Results Seven trials (6609 participants) were included. A dose-dependent superiority in lowering HbA1c was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from −17.71 mmol/mol (−1.62%) to −22.35 mmol/mol (−2.06%) vs placebo, −3.22 mmol/mol (−0.29%) to −10.06 mmol/mol (−0.92%) vs GLP-1 RAs, and −7.66 mmol/mol (−0.70%) to −12.02 mmol/mol (−1.09%) vs basal insulin regimens. Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg. Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin. Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06]), associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59]) and diarrhoea (OR 3.31 [95% CI 1.40, 7.85]). Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]). Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator, while all tirzepatide doses were safe in terms of serious adverse events and mortality. Conclusions/interpretation A dose-dependent superiority on glycaemic efficacy and body weight reduction was evident with tirzepatide vs placebo, GLP-1 RAs and basal insulin. Tirzepatide did not increase the odds of hypoglycaemia but was associated with increased incidence of gastrointestinal adverse events. Study limitations include presence of statistical heterogeneity in the meta-analyses for change in HbA1c and body weight, assessment of risk of bias solely for the primary outcome, and generalisation of findings mainly to individuals who are overweight or obese and already on metformin-based background therapy. PROSPERO registration no. CRD42021283449. Graphical abstract

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“…Various meta‐analyses have confirmed the favourable effect of SGLT‐2 inhibitors both on metabolic and cardiorenal endpoints in patients with type 2 diabetes 1,2,25‐27 . However, to our knowledge, no single study has to date assessed the effect of sotagliflozin on a series of efficacy and safety outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors reduce hyperglycaemia, body weight, and blood pressure, and display a beneficial effect on cardiovascular and renal endpoints in patients with type 2 diabetes 1,2 . Treatment guidelines recommend SGLT‐2 inhibitors in patients inadequately controlled with metformin monotherapy, particularly for those with heart failure or chronic kidney disease 3 .…”

Section: Introductionmentioning

confidence: 99%

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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Comparative efficacy of glucose‐lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta‐analysis

Cited by 103 publications

References 33 publications

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis

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

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