Sustained glucagon‐like peptide‐1 receptor agonist treatment improves glycemic control and reduces all‐cause mortality compared to dipeptidyl peptidase‐4 inhibitors: A real‐world target trial emulation in type 2 diabetes

Sørensen, KK; Yazdanfard, PDW; Zareini, B; Wood-Kurland, HK; Pedersen-Bjergaard, U; Andersen, MP; Michelsen, J; Imberg, H; Lind, M; Hallström, S; Lanzinger, S; Munch, A; Ohlendorff, JS; Gerds, TA; Torp-Pedersen, C; REDDIE Consortium

doi:10.1111/dom.70581

Type 2 & other diabetes

Sustained glucagon‐like peptide‐1 receptor agonist treatment improves glycemic control and reduces all‐cause mortality compared to dipeptidyl peptidase‐4 inhibitors: A real‐world target trial emulation in type 2 diabetes

Diabetes Obes MetabPublished 25 Feb 2026Target trial emulation

Main finding · Any HbA1c improvementResultAbsolute difference 15.7 % 95% CI 14.8%–16.5%

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Authors' conclusion

Within the limitations of this nationwide study and the available data, sustained GLP-1 RA therapy provided superior glycemic control and was associated with a modest mortality benefit compared with DPP-4i therapy.

Study context

Population: People with T2D initiating GLP-1 RA or DPP-4i, Danish nationwide registries (2012–2022)2.8 haemoglobin A1c (HbA1c) measurements per patient-year
Participants: 16,619 vs 34,196

Exposure: Sustained GLP-1 RA vs DPP-4i
GLP-1 RAn = 16,619
DPP-4in = 34,196reference
Outcome: Probability of improvement in defined HbA1c categories
Follow-up: Within 1 year

Methodological detailsnationwide registry-based cohort study, active comparator, Longitudinal Targeted Minimum Loss-based Estimation, controlling for baseline and time-varying confounding

Nationwide registry-based cohort study
Active comparator
Longitudinal Targeted Minimum Loss-based Estimation
Controlling for baseline and time-varying confounding

Main finding

Any HbA1c improvement · 1 year

Absolute difference

15.7 %

95% CI 14.8%–16.5%

By group

GLP-1 RA82.7%95% CI 82.0%–83.4%

DPP-4i67.1%95% CI 66.5%–67.6%

GLP-1 RAvs DPP-4i

absolute difference 15.7 % (95% CI 14.8%–16.5%)

As reported in the abstract

Observational data: associations, not effects.

Further findings

Outcome	Absolute reduction (%) (95% CI)
All-cause mortality · 1 yearLower with GLP-1 RA	0.4 (0.1%–0.7%)
All-cause mortality · 3 yearsLower with GLP-1 RA	1.1 (0.3%–2.0%)

Original publication

Sustained glucagon‐like peptide‐1 receptor agonist treatment improves glycemic control and reduces all‐cause mortality compared to dipeptidyl peptidase‐4 inhibitors: A real‐world target trial emulation in type 2 diabetes. Diabetes Obes Metab. Published 25 February 2026. doi:10.1111/dom.70581

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