Understanding Artificial Pancreas Systems: Results from a 24-Month Trial

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Open-label or unblinded (moderate): Open-label design

Industry funded (moderate): Industry funding reported

AMD: -3.67%; 95% CI -5.33, -2.01; p<0.001

At 26 weeks, canagliflozin lowered myocardial extracellular volume more than sitagliptin, with an adjusted mean difference of -3.67 percentage points. This was the primary endpoint and the clearest finding in the study.

AMD: -20.72 ml; 95% CI -36.30, -5.14; p=0.010

Canagliflozin improved left ventricular end-diastolic volume relative to sitagliptin at 26 weeks. The finding suggests favorable structural remodeling, although it was a secondary endpoint in a small trial.

AMD: -2.82 mm; 95% CI -4.95, -0.70; p=0.010

Echocardiography-derived left ventricular end-diastolic diameter favored canagliflozin at 26 weeks. This supports the structural remodeling signal seen with cardiac magnetic resonance measures.

Both groups showed comparable reductions in HbA1c (both Δ 0.7%, inter-group p=0.972)

Both groups lowered HbA1c by about 0.7%, and there was no clear between-group difference. This supports the interpretation that the cardiac imaging effects were not driven by stronger glucose lowering with canagliflozin.

LVEFCMR adjusted difference -1.42 (95% CI -5.51, 2.67), p=0.488

Left ventricular ejection fraction did not differ clearly between groups at 26 weeks. The study suggests structural changes rather than a clear systolic function benefit over this time frame.

Urinary tract infections occurred in 17.4% (4/23) of the canagliflozin group and 0% (0/22) of the sitagliptin group

Urinary tract infections were reported in 17.4% of the canagliflozin group and 0% of the sitagliptin group. This is directionally unfavorable for safety, although the study was small.

Oral SGLT2 inhibitor given at 100 mg/day for 26 weeks in adults with type 2 diabetes at high cardiovascular risk.

Both groups showed comparable reductions in HbA1c (both Δ 0.7%)

Sitagliptin reduced HbA1c by about 0.7% over 26 weeks, showing that the comparator provided similar glucose lowering to canagliflozin.

Oral DPP-4 inhibitor given at 100 mg/day for 26 weeks as the active comparator arm.

Positive: 4; Negative: 1; No effect: 2; Mixed: 0

Direction counts recalculated from intervention outcomes due to mismatch with AI-provided counts.

Extracted 7 outcome signals across the study

Primary imaging endpoint and two structural secondary endpoints favored canagliflozin, while glycemic change and ejection fraction showed no clear between-group difference and urinary tract infection rate was higher with canagliflozin.

Direction counts were recalculated from extracted outcomes because the AI-provided totals did not match.

Canagliflozin ↓ myocardial extracellular volume versus sitagliptin at 26 weeks

Mostly intermediate or surrogate outcomes

Primary cardiac MRI fibrosis marker favored canagliflozin over active comparator

Some structural remodeling measures improved, but systolic function measures did not clearly differ

Cardiac effects appeared separate from glucose lowering because HbA1c reductions were similar in both groups

Yan H, Liu J, Zhang Z, et al. Canagliflozin attenuates CMR-quantified myocardial fibrosis in individuals with type 2 diabetes mellitus at high cardiovascular risk: a randomised open-label controlled trial. Diabetologia. 2026;69(6):1532-1544. doi:10.1007/s00125-026-06682-w

Small single-center trial with 45 randomized participants

Open-label design may introduce bias despite blinded outcome assessment

Main findings rely on surrogate imaging markers rather than clinical cardiovascular events

In a 26-week randomized trial, canagliflozin reduced CMR-measured myocardial extracellular volume and improved some left ventricular structural measures versus sitagliptin in adults with type 2 diabetes at high cardiovascular risk.

Canagliflozin ↓ left ventricular end-diastolic volume and diameter

HbA1c ↓ similarly in both groups, with no clear between-group difference

Participants received canagliflozin 100 mg/day for 26 weeks; baseline glucose-lowering medications remained unchanged.

Canagliflozin 100 mg/day

Participants received sitagliptin 100 mg/day for 26 weeks; baseline glucose-lowering medications remained unchanged.

Sitagliptin 100 mg/day

Limited population scope (moderate): Narrow population scope

Limited safety reporting (moderate): Safety reporting depth: limited

No post-intervention follow-up (moderate): 0 weeks of follow-up after treatment ended

Canagliflozin may reduce myocardial fibrosis in high-risk type 2 diabetes

This trial compared canagliflozin with sitagliptin in adults with type 2 diabetes and high cardiovascular risk. Over 26 weeks, canagliflozin lowered a cardiac MRI marker linked to myocardial fibrosis and improved some measures of heart structure, while blood sugar lowering was similar in both groups.

This was a 26-week study, so long-term durability is unknown

The study used an active comparator rather than placebo

Most participants were Han Chinese from one tertiary center in Shanghai

The trial was not designed to prove fewer heart failure events or deaths

Canagliflozin versus sitagliptin for cardiac remodeling in high-risk type 2 diabetes

Canagliflozin may reduce myocardial fibrosis in high-risk type 2 diabetes

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