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

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CFB in HbA1c was -1.44% (SE 0.07) for tirzepatide vs -0.67% (SE 0.08) for dulaglutide at week 40 (treatment-regimen estimand). Estimated treatment difference -0.77% (95% CI -0.98 to -0.56, p<0.001).

Tirzepatide reduced HbA1c consistently across all baseline subgroups with mean reductions of 1.44% (SE 0.07) at week 40. Treatment differences versus dulaglutide ranged from -0.7% to -1.2% across subgroups. HbA1c reduction was numerically greater in participants with higher baseline HbA1c (>8.5%) and lower BMI (<27 kg/m²).

CFB in body weight was -10.5 kg (SE 0.5) for tirzepatide vs -3.6 kg (SE 0.5) for dulaglutide at week 40 (treatment-regimen estimand). Estimated treatment difference -6.9 kg (95% CI -8.3 to -5.5, p<0.001).

Tirzepatide reduced body weight consistently across all baseline subgroups with mean reductions of 10.5 kg (SE 0.5) at week 40. Treatment differences versus dulaglutide ranged from -5.7kg to -8.6kg across subgroups. Weight reduction was significantly greater in non-Hispanic/Latino participants compared to Hispanic/Latino participants.

Overall AE incidence: 72.7% tirzepatide vs 73.4% dulaglutide. Numerically higher in ≥65 years: 82.9% tirzepatide vs 81.1% dulaglutide.

Overall incidence of adverse events was similar between tirzepatide (72.7%) and dulaglutide (73.4%) treatment groups. The frequency was generally consistent across baseline subgroups, though numerically higher in participants aged ≥65 years (82.9% tirzepatide, 81.1% dulaglutide) compared to <65 years (69.2% tirzepatide, 70.8% dulaglutide).

Nausea: 25.2% tirzepatide vs 18.9% dulaglutide. Diarrhea: 22.3% tirzepatide vs 13.3% dulaglutide. Most commonly reported TEAEs in each subgroup.

Gastrointestinal adverse events were the most commonly reported treatment-emergent adverse events. Nausea occurred in 25.2% of tirzepatide participants versus 18.9% of dulaglutide participants. Diarrhea occurred in 22.3% of tirzepatide participants versus 13.3% of dulaglutide participants. These were generally well-tolerated across subgroups.

Dual GIP/GLP-1 receptor agonist, escalated from 2.5mg to 15mg or maximum tolerated dose over 40 weeks via once-weekly subcutaneous injection

{"intervention_arm_id":"arm_2","reference_arm_ids":["arm_1"],"comparison_type":"head_to_head"}

CFB in HbA1c was -0.67% (SE 0.08) for dulaglutide at week 40 (treatment-regimen estimand).

Dulaglutide dose escalation reduced HbA1c across all baseline subgroups with mean reduction of 0.67% (SE 0.08) at week 40, though significantly less than tirzepatide. HbA1c reduction was numerically greater in participants with higher baseline HbA1c (>8.5%).

CFB in body weight was -3.6 kg (SE 0.5) for dulaglutide at week 40 (treatment-regimen estimand).

Dulaglutide dose escalation reduced body weight across all baseline subgroups with mean reduction of 3.6 kg (SE 0.5) at week 40, though significantly less than tirzepatide. Weight reduction was consistent across most subgroups.

GLP-1 receptor agonist, dose escalated from baseline (0.75mg or 1.5mg) to 4.5mg or maximum tolerated dose over 40 weeks via once-weekly subcutaneous injection

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

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

Extracted 6 outcome signals across the study

Tirzepatide showed consistent superiority over dulaglutide dose escalation for both primary (HbA1c) and key secondary (body weight) outcomes across all prespecified baseline subgroups.

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

HbA1c ↓ greater with tirzepatide vs dulaglutide across all subgroups (difference -0.7% to -1.2%)

Mostly intermediate or surrogate outcomes

Tirzepatide switching provided consistent HbA1c and weight reductions regardless of age, sex, ethnicity, diabetes duration, BMI, baseline HbA1c, or dulaglutide dose/duration

HbA1c reductions were numerically larger in participants with higher baseline HbA1c (>8.5%) and lower BMI (<27 kg/m²)

Weight reduction was significantly greater in non-Hispanic/Latino participants compared to Hispanic/Latino participants

Violante-Ortiz R, Rose L, Sharma P, et al. Safety and efficacy of switching from dulaglutide to tirzepatide across clinically relevant baseline characteristics in participants with T2D: subgroup analysis of SURPASS-SWITCH. BMJ Open Diabetes Res Care. 2026;14(2):e005711. doi:10.1136/bmjdrc-2025-005711

Open-label study design may introduce bias

Limited sample sizes in some subgroups (e.g., BMI <27 kg/m²: n=27)

Study not powered for subgroup analyses or safety comparisons

Multiple subgroup testing increases risk of false-positive findings

Switching to tirzepatide from dulaglutide resulted in consistently greater HbA1c and weight reductions versus dulaglutide dose escalation across all baseline subgroups in adults with T2D.

Body weight ↓ greater with tirzepatide vs dulaglutide across all subgroups (difference -5.7 to -8.6 kg)

Adverse events rates similar between treatments, with GI symptoms (nausea, diarrhea) most common

Participants switched to tirzepatide 2.5 mg and escalated to 15 mg or MTD. Dose escalations performed every 4 weeks using single-dose pen. 79.9% achieved maximum dose of 15mg.

Tirzepatide

Participants continued dulaglutide and escalated to 4.5 mg or MTD. Baseline doses were 0.75mg (33.3%) or 1.5mg (66.7%). Dose escalations performed every 4 weeks using single-dose pen. 89.5% achieved maximum dose of 4.5mg.

Dulaglutide

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

Relies on surrogate outcomes (moderate): No hard clinical outcomes reported

Switching to tirzepatide from dulaglutide improved HbA1c and weight across baseline characteristics

This subgroup analysis of SURPASS-SWITCH found that switching to tirzepatide from dulaglutide provided greater improvements in blood sugar control and weight loss compared to escalating dulaglutide dose, with consistent benefits across all patient groups including different ages, baseline HbA1c levels, diabetes duration, BMI categories, and ethnicities.

Results represent a subgroup analysis; interpret with caution given multiple comparisons

Open-label design means participants and clinicians knew which treatment was assigned

Safety profile similar across groups, but older adults (≥65 years) had higher adverse event rates

Hypoglycemia rates were higher with tirzepatide, particularly in those with lower BMI and higher baseline HbA1c

Ethnic differences in weight loss response may reflect genetic, cultural, or lifestyle factors requiring further study

Efficacy and safety of switching to tirzepatide versus escalating dulaglutide dose across baseline patient characteristics

Adults with type 2 diabetes on dulaglutide 0.75mg or 1.5mg with HbA1c 7.0-9.5%

Patients on stable doses of 0-3 oral antihyperglycemic medications (metformin, sulfonylurea, or SGLT2 inhibitor)

Individuals with BMI ≥25 kg/m² not achieving glycemic control on current therapy

Intervention	Outcome	Measured Change	Study Effect
Dulaglutide dose escalation (Medications)	Body weight (Weight & Anthropometrics)	Decrease	Limited
Dulaglutide dose escalation (Medications)	HbA1c (Glycemic Control)	Decrease	Mixed
Tirzepatide (Medications)	Adverse events incidence (Safety)	Uncertain	Mixed
Tirzepatide (Medications)	Body weight (Weight & Anthropometrics)	Decrease	Strong
Tirzepatide (Medications)	Gastrointestinal disorders incidence (Safety)	Increase	Mixed
Tirzepatide (Medications)	HbA1c (Glycemic Control)	Decrease	Strong

Switching to tirzepatide from dulaglutide improved HbA1c and weight across baseline characteristics

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