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DPP-4 inhibitors (DPP-4i) and sulphonylureas remain the most widely prescribed add-on treatments after metformin. However, there is limited evidence from clinical practice comparing major adverse cardiovascular events (MACE) in patients prescribed these treatments, particularly among those without prior history of MACE and from vulnerable population groups. Using electronic health records from UK primary care, we undertook a retrospective cohort study with people diagnosed type-2 diabetes mellitus, comparing incidence of MACE (myocardial infarction, stroke, major cardiovascular surgery, unstable angina) and all-cause mortality among those prescribed DPP-4i versus sulphonylureas as add-on to metformin. We stratified analysis by history of MACE, age, social deprivation and comorbidities and adjusted for HbA1c, weight, smoking-status, comorbidities and medications. We identified 17,570 patients prescribed sulphonylureas and 6,267 prescribed DPP-4i between 2008-2017. Of these, 16.3% had pre-existing MACE. Primary incidence of MACE was similar in patients prescribed DPP-4i and sulphonylureas (10.3 vs 8.5 events per 1000 person-years; adjusted Hazard Ratio (adjHR): 0.94; 95%CI 0.80-1.14). For those with pre-existing MACE, rates for recurrence were higher overall, but similar between the two groups (21.8 vs 17.2 events per 1000 person-years; adjHR: 0.93; 95%CI 0.69-1.24). For those aged over 75 and with BMI less than 25 kg/m 2 there was a protective effect for DPP-I, warranting further investigation. Patients initiating a DPP-4i had similar risk of cardiovascular outcomes to those initiating a sulphonylurea. This indicates the choice should be based on safety and cost, not cardiovascular prognosis, when deciding between a DPP-4i or sulphonylurea as add-on to metformin., (© 2021. The Author(s).)

Background two common anti-diabetic treatments used are sitagliptin and sulphonylureas however evidence examining their comparative effectiveness in older people is limited. Objective to evaluate effectiveness of sitagliptin vs sulphonylureas when added to metformin in older (aged ≥75) vs younger people (18–75). Design retrospective cohort study. Setting UK Primary Care. Subjects 2,904 individuals prescribed sitagliptin (223 aged≥75) and 13,683 prescribed sulphonylureas (1,725 aged ≥75). Methods multivariable regression to analyse difference in HbA1c and weight, 12 months after add-on initiation and proportion achieving different glycaemic targets. Results after multivariate adjustment to remove baseline differences, the HbA1c after 12 months of treatment was on average 1 mmol/mol (95%CI −0.7 to 2.8) higher with sitagliptin vs sulphonylureas in older people though this was not statistically significant. The weight however, was significantly lower −1.4 kg (95%CI −2.1 to −0.7) with sitagliptin vs sulphonylureas. A lower proportion prescribed sitagliptin vs sulphonylureas recorded HbA1c < 48 mmol/mol by study end: Odds Ratio 0.63 (95%CI 0.42–0.95). In younger people, similar HbA1c reductions were also observed with both treatments, however weight after 12 months was even lower with sitagliptin vs sulphonylureas: −2.3 kg (95%CI −2.5 to −2.0). Conclusions similar HbA1c reduction was observed when sitagliptin or sulphonylureas were added to metformin in older and younger age-groups. Sitagliptin use led to modest comparative weight loss. There may be greater risk of over-treatment with sulphonylureas evidenced by greater proportion recording HbA1c < 48 mmol/mol by study end. This evidence supporting use of sitagliptin when add-on therapy is selected in older adults should be considered alongside the wider evidence-base and patient-preference. [ABSTRACT FROM AUTHOR]