Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention: A Randomized Trial: Annals of Internal Medicine: Vol 177, No 11

Background: REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) led to new guidelines for statin use among people with HIV (PWH) with low to moderate risk for atherosclerotic cardiovascular disease (ASCVD). Little is known about the natural history of diabetes mellitus (DM) or mechanisms contributing to statin effects on DM among this population. Objective: To determine the contribution of known DM risk factors to excess risk for DM with pitavastatin in REPRIEVE. Design: Phase 3, primary ASCVD prevention trial over a median of 5.6 years of follow-up. (ClinicalTrials.gov: NCT02344290) Setting: Global, multicenter trial. Participants: 7731 PWH aged 40 to 75 years with low to moderate ASCVD risk (by the pooled cohort equations from the American College of Cardiology and American Heart Association) without DM at study entry. Intervention: Random 1:1 assignment to pitavastatin, 4 mg daily, or placebo. Measurements: New-onset DM was determined at each visit by clinical diagnosis requiring initiation of medication treatment for DM. The incidence of new-onset DM was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. Treatment effects of pitavastatin on progression to new DM in key subgroups were determined. Results: Participants with at least 3 DM risk factors (vs. no risk factors) had increased risk for DM in each treatment group (incidence rate, 3.24 per 100 person-years [PY] vs. 0.34 per 100 PY [pitavastatin] and 2.66 per 100 PY vs. 0.27 per 100 PY [placebo]). The incidence of DM was highest in South Asia. In adjusted analyses, high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset DM (all P < 0.005). Limitation: Pitavastatin was the only statin assessed; DM was assessed clinically. Conclusion: Metabolic risk factors, including prediabetes and obesity, contributed to new-onset DM in statin- and placebo-treated participants. A clinically significant effect of pitavastatin on DM was seen primarily among those with multiple risk factors for DM at entry. Strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against DM among PWH. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes: Two Target Trial Emulation Studies: Annals of Internal Medicine: Vol 178, No 7

Background: Reduction of premature death and adverse cardiovascular outcomes is a key goal in type 2 diabetes management. Objective: To compare mortality and cardiovascular event risks in patients treated with semaglutide versus empagliflozin and, secondarily, dulaglutide versus empagliflozin. Design: Target trial emulation studies from observational data comparing semaglutide- or dulaglutide-treated patients with propensity score–matched patients treated with empagliflozin. Setting: Health care system of 703 academic and community clinical practices. Participants: Patients aged 45 years or older with type 2 diabetes treated from 1 January 2019 to 31 December 2024 with semaglutide, dulaglutide, or empagliflozin. Intervention: Initial treatment with semaglutide, dulaglutide, or empagliflozin. At baseline, concomitant treatment with other diabetes medication was permitted, excluding other glucagon-like peptide-1 receptor agonists or sodium–glucose cotransporter-2 inhibitors. Measurements: A composite of death, myocardial infarction (MI), or stroke was the primary outcome, and secondary composite outcomes included death or MI, MI or stroke, and individual cardiac events. Results: Patients treated with semaglutide (n = 7899) versus empagliflozin (n = 7899) were followed for a median of 2.2 years; the respective rates of the composite of death, MI, or stroke were 3.7% versus 4.5% at 2 years and 5.9% versus 6.9% at 3 years. Corresponding incidence rates for the composite outcome were 20.99 versus 23.56 per 1000 person-years, with a hazard ratio (HR) of 0.89 (95% CI, 0.78 to 1.02). The HRs for the individual outcomes were 0.97 (CI, 0.81 to 1.15) for death, 0.85 (CI, 0.68 to 1.05) for MI, and 0.62 (CI, 0.43 to 0.89) for stroke. Risks for dulaglutide- and empagliflozin-treated patients were similar for the composite outcome (HR, 1.03 [CI, 0.90 to 1.16]) and for death, MI, and stroke separately. Limitation: Observational study design, lack of data on cause-specific mortality, and residual confounding. Conclusion: Semaglutide treatment seems to confer some advantage over empagliflozin. This advantage was not observed for dulaglutide. Primary Funding Source: American Heart Association.

Newer Pharmacologic Treatments for Type 2 Diabetes

Health Expenditures of Patients With Diabetes After Bariatric Surgery: Comparing Gastric Bypass and Sleeve Gastrectomy

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differ in their effects on body weight and risk for reoperation. However, it is unclear whether long-term health expenditures differ by procedure type in patients with diabetes. Objective: To compare health expenditures 3 years before and 5.5 years after bariatric surgery between patients with diabetes undergoing RYGB versus SG. Design: Retrospective cohort study using target trial emulation principles. Setting: Integrated health system. Patients: Patients with diabetes undergoing RYGB (n = 3147) or SG (n = 3510) from 2012 to 2019. Measurements: Total, inpatient, outpatient, and medication expenditures. Results: Characteristics of patients undergoing RYGB and SG were well balanced after weighting; 73% were female, average body mass index was 43.8 kg/m2, and average age was 50 years. Expenditures per 6-month period decreased by about 30% for both groups, from $4039.06 (95% CI, $3770.88 to $4326.31) 3 years before to $2441.13 (CI, $2151.07 to $2770.30) 5.5 years after RYGB and from $3918.37 (CI, $3658.75 to $4196.40) 3 years before to $2658.15 (CI, $2279.17 to $3100.16) 5.5 years after SG. Total expenditures after surgery did not differ between groups through 5.5 years (difference at 5.5 years, −$217.02 [CI, −$671.29 to $201.96]) except for the first 6 months, when expenditures were transiently higher in the RYGB group (difference, $564.32 [CI, $232.60 to $895.20]), driven by a higher inpatient admission rate. Otherwise, postsurgical outpatient and medication expenditures did not appear to differ between RYGB and SG. Limitation: Unobserved confounding. Conclusion: Overall expenditures decreased substantially in the postsurgical period, primarily due to reductions in pharmacy expenditures, with no differences between RYGB and SG except in the first 6 months after surgery. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

Type 2 Diabetes

Type 2 diabetes (T2D) is a prevalent disease that increases risk for vascular, renal, and neurologic complications. Prevention and treatment of T2D and its complications are paramount. Many advancements in T2D care have emerged over the past 5 years, including increased understanding of the importance of early intensive glycemic control, mental health, social determinants of health, healthy eating patterns, continuous glucose monitoring, and the benefits of some drugs for preventing cardiorenal disease. This review summarizes the evidence supporting T2D prevention and treatment, focusing on aspects that are commonly in the purview of primary care physicians.

Type 2 Diabetes

Type 2 diabetes is a prevalent illness that causes major vascular, renal, and neurologic complications. Prevention and treatment of diabetes and its complications are of paramount importance. Many new treatments have emerged over the past 5–10 years. Recent evidence shows that newer treatments may substantially reduce risk for cardiac and renal disease, suggesting that it may be necessary to change existing treatment paradigms. This review summarizes the evidence supporting diabetes prevention and treatment, focusing on aspects that are commonly in the purview of primary care physicians.

Review: In adults with type 1 diabetes, SGLT-2 inhibitors reduce HbA1c but increase diabetic ketoacidosis

Source Citation Yamada T, Shojima N, Noma H, Yamauchi T, Kadowaki T. Sodium–glucose co-transporter-2 inhibitors as add-on therapy to insulin for type 1 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2018;20:1755-61. 29451721

Review: In type 2 diabetes, SGLT-2 inhibitors or GLP-1 agonists reduce mortality vs control or DPP-4 inhibitors

Source Citation Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association between use of sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018;319:1580-91. 29677303

In diabetes with no CVD, aspirin reduced serious vascular events but increased major bleeding at 7.4 years

Source Citation ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379:1529-39. 30146931

Risk scores overestimated risk for CVD in newly diagnosed type 2 diabetes

Source Citation Read SH, van Diepen M, Colhoun HM, et al; Scottish Diabetes Research Network Epidemiology Group. Performance of cardiovascular disease risk scores in people diagnosed with type 2 diabetes: external validation using data from the National Scottish Diabetes Register. Diabetes Care. 2018;41:2010-18. 30002197