In high-risk type 2 diabetes, adding oral semaglutide to standard care reduced MACE at a mean 48 mo

Clinical Impact Ratings GIM/FP/GP: 6 out of 7 Cardiology: 6 out of 7 Endocrinology: 5 out of 7 Nephrology: 6 out of 7

In type 2 diabetes with CKD and additional CV risk factors, sotagliflozin reduced total MACE vs. placebo at a median 14 mo

Clinical Impact Ratings GIM/FP/GP: 6 out of 7 Cardiology: 5 out of 7 Endocrinology: 5 out of 7 Nephrology: 6 out of 7

Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes

Background: The comparative gastrointestinal safety across glucagon-like peptide-1 receptor agonists and tirzepatide is still unclear. Objective: To compare the risk for severe gastrointestinal adverse events across dulaglutide, subcutaneous semaglutide, and tirzepatide in patients with type 2 diabetes (T2D) in routine clinical practice. Design: New-user, active-comparator cohort study. Setting: Population-based study. Participants: Adults with T2D initiating dulaglutide, subcutaneous semaglutide, and tirzepatide between 1 January 2019 and 30 August 2024 in 3 cohorts corresponding to 3 pairwise comparisons. Measurements: The primary outcome was a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation. Secondary outcomes of interest were the individual components of the primary outcome. Patients were 1:1 propensity score matched within each comparison. We calculated hazard ratios (HRs) with 95% CIs. Results: There were 65 238 matched pairs in the semaglutide versus dulaglutide cohort, 20 893 in the tirzepatide versus dulaglutide cohort, and 46 620 in the tirzepatide versus semaglutide cohort. The HR of gastrointestinal events was 0.96 (95% CI, 0.87 to 1.06) in the semaglutide versus dulaglutide cohort, 0.96 (CI, 0.77 to 1.20) in the tirzepatide versus dulaglutide cohort, and 1.07 (CI, 0.90 to 1.26) in the tirzepatide versus semaglutide cohort. Limitation: Possible residual confounding by glycemic control and body mass index. Conclusion: These findings suggest that dulaglutide, semaglutide, and tirzepatide have similar gastrointestinal safety profiles in adults with T2D. This study provides clinicians with evidence to weigh the benefits and risks of these medications. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

Annals On Call - Health Expenditures of Patients With Diabetes After Bariatric Surgery

In adults with overweight or obesity and without diabetes, GLP-1 RAs increase weight loss vs. placebo

Clinical Impact Ratings GIM/FP/GP: 5 out of 7 Endocrinology: 5 out of 7

Effectiveness and Safety of Statins in Type 2 Diabetes According to Baseline Cardiovascular Risk: A Target Trial Emulation Study: Annals of Internal Medicine: Vol 179, No 2

Background: Whether statins benefit patients with type 2 diabetes mellitus (T2DM) with low predicted 10-year cardiovascular risk is uncertain. Objective: To evaluate the effectiveness and safety of statin initiation for primary prevention among adults with T2DM stratified by predicted 10-year risk for cardiovascular disease (CVD). Design: Cohort study using target trial emulation. Setting: U.K. primary care using the IQVIA Medical Research Data database. Participants: Persons aged 25 to 84 years with a diagnosis of T2DM between 2005 and 2016 and no history of coronary artery disease, myocardial infarction, stroke, heart failure, myopathy, liver disease, rheumatic heart disease, schizophrenia, or cancer. Intervention: Statin initiation versus noninitiation, with estimation of the observational analogues of the intention-to-treat effect. Statin initiators were propensity score–matched to noninitiators in a 1:4 ratio within 4 QRISK3 strata of 10-year predicted cardiovascular risk: low (<10%), intermediate (10% to 19%), high (20% to 29%), and very high (≥30%). Measurements: Absolute risk differences (RDs) and risk ratios (RRs) at 10 years of follow-up for all-cause mortality and major CVD, as well as myopathy and liver dysfunction. Results: Statin initiation was associated with reductions in all-cause mortality and major CVD across QRISK3 strata. In the low-risk stratum, RDs and RRs were −0.53% (95% CI, −0.90% to −0.08%) and 0.80 (95% CI, 0.67 to 0.97), respectively, for all-cause mortality and −0.83% (95% CI, −1.28% to −0.34%) and 0.78 (95% CI, 0.66 to 0.91), respectively, for major CVD. A small increased risk for myopathy was observed in the moderate-risk stratum only, and there was no associated increased risk for liver dysfunction in any stratum. Limitations: Unmeasured confounding and underascertainment of some hospitalization outcomes. Conclusion: Statin use in T2DM for primary prevention was associated with reductions in all-cause mortality and major CVD across the full spectrum of predicted cardiovascular risk. Primary Funding Source: National Natural Science Foundation of China.

Association of Weekend Warrior and Other Physical Activity Patterns With Mortality Among Adults With Diabetes: A Cohort Study: Annals of Internal Medicine: Vol 178, No 9

Background: “Weekend warrior” and regularly active physical activity patterns have been associated with reduced mortality risk in the general population. The association in patients with diabetes is unknown. Objective: To examine the associations of different physical activity patterns, particularly weekend warrior and regularly active behavior, with all-cause, cardiovascular, and cancer mortality among adults with diabetes. Design: Prospective cohort study. Setting: National Health Interview Survey (1997 to 2018) linked to the National Death Index records through 31 December 2019. Participants: 51 650 U.S. adults with self-reported diabetes. Measurements: Participants categorized by 4 physical activity groups: inactive (reporting no moderate-to-vigorous physical activity [MVPA]), insufficiently active (MVPA <150 minutes per week), weekend warrior (MVPA ≥150 minutes per week in 1 to 2 sessions), and regularly active (MVPA ≥150 minutes per week in ≥3 sessions). Results: During a median follow-up of 9.5 years, 16 345 deaths (cardiovascular, 5620; cancer, 2883) were documented. Compared with inactive participants, multivariable-adjusted hazard ratios (HRs) for all-cause mortality were significantly lower across physical activity groups: insufficiently active persons (HR, 0.90 [95% CI, 0.85 to 0.95]), weekend warriors (HR, 0.79 [CI, 0.69 to 0.91]), and regularly active persons (HR, 0.83 [CI, 0.78 to 0.87]). These reductions were mostly due to benefits with cardiovascular mortality: insufficiently active persons (HR, 0.98 [CI, 0.89 to 1.07]), weekend warriors (HR, 0.67 [CI, 0.52 to 0.86]), and regularly active persons (HR, 0.81 [CI, 0.74 to 0.88]). There were fewer differences by cancer mortality: insufficiently active persons (HR, 0.88 [CI, 0.78 to 1.00]), weekend warriors (HR, 0.99 [CI, 0.76 to 1.30]), and regularly active persons (HR, 0.85 [CI, 0.75 to 0.96]). Limitation: Physical activity was self-reported and assessed at a single time point. Conclusion: Weekend warrior and regularly active physical activity patterns meeting current physical activity recommendations (MVPA ≥150 minutes per week) were associated with 21% and 17% lower risks for all-cause mortality and 33% and 19% lower hazards of cardiovascular mortality among adults with diabetes compared with those with diabetes who are physically inactive. Primary Funding Source: Capital’s Funds for Health Improvement and Research, and National Natural Science Foundation of China.

Treatment With Canagliflozin Versus Placebo in Children and Adolescents With Type 2 Diabetes: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 9

Background: Treatment options for children and adolescents with type 2 diabetes mellitus (T2DM) are limited. Canagliflozin is a sodium–glucose cotransporter-2 inhibitor approved for the treatment of T2DM in adults. Objective: To assess the safety and efficacy of canagliflozin in children and adolescents with T2DM. Design: Phase 3, randomized, double-blind, placebo-controlled, parallel-group study. (ClinicalTrials.gov: NCT03170518; EudraCT: 2016-005223-88) Setting: Multicenter (104 sites in 10 countries). Participants: Children and adolescents aged 10 years or older with T2DM (hemoglobin A1c [HbA1c] ≥6.5% to ≤11%). Intervention: Participants were randomly assigned to canagliflozin (100 mg) or placebo once daily. Participants with week 12 readings of 7% or higher for HbA1c and at least 60 mL/min/1.73 m2 for estimated glomerular filtration rate were randomly assigned again at week 13 to either keep receiving 100 mg of canagliflozin (or placebo) or have their dose uptitrated to 300 mg (or placebo). The treatment period was 52 weeks. Measurements: Change in HbA1c from baseline to week 26 (primary efficacy end point), secondary efficacy end points, and safety. Results: A total of 171 participants were randomly assigned to canagliflozin (n = 84) or placebo (n = 87). At week 26, HbA1c reduction from baseline was significantly greater with canagliflozin than placebo (difference in least-squares means, −0.76% [95% CI, −1.25% to −0.27%]; P = 0.002). The proportion of participants who achieved HbA1c levels below 6.5% was significantly greater with canagliflozin than placebo (36.3% vs. 14.0%; difference, 22.3 percentage points [CI, 10.5 to 34.1 percentage points]). Treatment-emergent adverse events (AEs) occurred in 77.4% and 74.7% and serious treatment-emergent AEs in 9.5% and 5.7% of participants who received canagliflozin and placebo, respectively. Common AEs seen with canagliflozin were similar to those in the adult population. Hypoglycemia occurred in 11.9% and 10.3% of participants receiving canagliflozin and placebo, respectively. Limitation: Study duration and relatively small sample size. Conclusion: In children and adolescents with T2DM, canagliflozin provided a clinically meaningful reduction in HbA1c, with a safety profile similar to that seen in adults. Primary Funding Source: Johnson & Johnson.

Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 5

Background: Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for the treatment of adults with type 2 diabetes or obesity, showed clinically meaningful reductions in hemoglobin A1c (HbA1c) and body weight in the SURPASS phase 3 clinical trial program. Objective: To compare efficacy and safety of escalation of dulaglutide dose versus switching to tirzepatide in inadequately controlled type 2 diabetes. Design: Multicenter, randomized, open-label, phase 4 trial (SURPASS-SWITCH [A Phase 4, Randomized, Open-Label, Active-Controlled Study to Investigate the Efficacy and Safety of Switching from Weekly Dulaglutide to Weekly Tirzepatide in Adults with Type 2 Diabetes], ClinicalTrials.gov: NCT05564039). Setting: 38 sites across 5 countries. Participants: Adults with HbA1c 7.0% or greater to 9.5% or less, stable body weight, body mass index of 25 kg/m2 or greater, receiving a stable dose of dulaglutide (0.75 or 1.5 mg) for at least 6 months and 0 to 3 oral antihyperglycemic medications for at least 3 months. Intervention: Escalation of dulaglutide to 4.5 mg or maximum tolerated dose (MTD) or switching to tirzepatide. Measurements: The primary end point was change from baseline in HbA1c at week 40. The key secondary end point was change from baseline in weight at week 40. Results: A total of 282 adults were randomly assigned to tirzepatide (n = 139) or dulaglutide (n = 143). Change from baseline in HbA1c at week 40 was −1.44% (SE, 0.07) with tirzepatide, 15 mg or MTD, and −0.67% (SE, 0.08) with dulaglutide, 4.5 mg or MTD (estimated treatment difference, −0.77% [95% CI, −0.98% to −0.56%; P < 0.001]). Change from baseline in weight at week 40 was −10.5 kg (SE, 0.5) with tirzepatide and −3.6 kg (SE, 0.5) with dulaglutide (estimated treatment difference, −6.9 kg [CI, −8.3 to −5.5 kg; P < 0.001]). Serious adverse events were reported by 10 (7.2%) tirzepatide and 10 (7.0%) dulaglutide participants. The most common treatment-emergent adverse events were nausea and diarrhea. Limitation: Open-label design. Conclusion: In SURPASS-SWITCH, switching treatment to tirzepatide provided additional HbA1c reduction and weight loss compared with escalating treatment with dulaglutide. Primary Funding Source: Eli Lilly and Company.

Quality Indicators for Diabetes in Adults: A Review of Performance Measures by the American College of Physicians

Type 1 and type 2 diabetes are prevalent chronic illnesses, are leading causes of mortality and morbidity, and result in substantial public health burden. Timely identification and appropriate management of diabetes can help reduce adverse consequences of diabetes. The American College of Physicians (ACP) embraces performance measurement as a means to improve quality of care but believes that a performance measure must be methodologically sound and evidence-based in order to be considered for inclusion in payment, accountability, or reporting programs. These principles are critical given the potential impact on physician administrative work, reputation, and reimbursement and to prevent unintended consequences for patient care. To help improve performance measurement and reduce burden, the ACP Performance Measurement Committee (PMC) reviews performance measures using a rigorous process to recognize high-quality measures and address gaps and areas for improvement. In this article, the PMC presents its review of 14 current performance measures for diabetes that are relevant to internal medicine. The PMC supports kidney health evaluation at the individual and group practice levels, hemoglobin A1c control at the health plan level, eye examination at the health plan level, and angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy at the individual physician level.