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Empagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long-term safety and effect of empagliflozin on cardiovascular outcomes.

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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

ObjectiveTo assess the efficacy of the Diabetes Medication Choice Decision Aid among patients with type 2 diabetes in Greece.DesignOpen-label cluster randomised controlled trial.SettingPrimary and secondary care practices across Greece.Participants5 sites allocated to the decision aid (n=101 patients) and 4 sites to control (n=103 patients).InterventionClinicians and patients in the intervention arm used a decision aid, based on outcomes that both consider important when choosing among antihyperglycaemic medications. Patients in the control arm received usual care.Outcome measuresThe primary outcome was patient's level of decisional comfort after the initial clinical encounter. Secondary outcomes included patient's knowledge about type 2 diabetes and medications, and patient's and clinician's satisfaction. Adherence to prescribed antihyperglycaemic medication and change in glycated haemoglobin were assessed at 24 weeks.ResultsPatients in both arms had similar scores in overall decisional comfort (mean difference between the usual care and decision aid arms −6.9, 95% CI −21.5 to 7.7) and its subscales. Patients' knowledge was high in both arms (mean difference 2.3%, 95% CI −15.7% to 20.4%). Patients and clinicians in both groups were equally satisfied with the decision-making. No significant difference in medication adherence and glycaemic control was found across arms. Clinicians found the decision aid useful and reported that its integration in their daily routine was easy.ConclusionsThe decision aid was implemented and positively received in the clinical setting in Greece, in line with the patient-centred approach endorsed by current guidelines. However, this trial yielded imprecise results in terms of patient outcomes. Further research is needed to investigate the interaction between the patient and the clinician in order to clarify the association between the use of decision aids and implementation of shared decision-making.Trial registration numberNCT01861756. Pre-results.

Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.

Aim To compare the effects of glucose‐lowering drugs on body weight and blood pressure in adults with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library, and grey literature sources until 29 September 2020 for randomized controlled trials of at least 24 weeks' duration assessing the effects of glucose‐lowering drugs on body weight and blood pressure in adults with type 2 diabetes. We performed frequentist network meta‐analyses and calculated weighted mean differences and 95% confidence intervals combining trial arms of different approved doses of a given intervention into a single group. We evaluated the confidence in pooled estimates using the CINeMA (Confidence In Network Meta‐Analysis) framework. Results In total, 424 trials (276 336 patients) assessing 21 antidiabetic medications from nine drug classes were included. Subcutaneous semaglutide was the most efficacious in reducing body weight followed by oral semaglutide, exenatide twice‐daily, liraglutide, and the sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin. The same agents also conferred the greatest reductions in systolic blood pressure. Metformin had a modest effect in reducing body weight and systolic blood pressure. Diastolic blood pressure was reduced with the SGLT‐2 inhibitors pioglitazone, exenatide twice‐daily and semaglutide. In subgroup analyses of trials with over 52 weeks' duration, semaglutide and SGLT‐2 inhibitors reduced both body weight and systolic blood pressure. Conclusions Semaglutide and SGLT‐2 inhibitors conferred reductions both in body weight and blood pressure that were sustainable for over 1 year of treatment. These agents may be preferable treatment options for patients with type 2 diabetes who are overweight/obese and/or hypertensive.