Last updated July 4, 2026
Key finding
cIMT thickness in subjects receiving conventional therapy increased significantly by +0.017 mm.
This study evaluated the efficacy and durability of initial combination therapies for Type 2 Diabetes, finding that initial triple therapy showed lower liver fat content compared to sequential therapy.
Quick read
The essential study design details in one scan.
EvidenceScore™
Moderate
Study type
RCTs
Follow-up
Extended (5–20+ y)
Risk of bias
Some Concerns
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Plain-language summary
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Study focus
This study evaluated the efficacy and durability of initial combination therapies for Type 2 Diabetes, finding that initial triple therapy showed lower liver fat content compared to sequential therapy.
Understanding the differences in outcomes between these two treatment approaches is crucial for clinicians managing Type 2 Diabetes. The findings suggest that initial triple therapy may offer benefits in terms of liver health, which is significant given the association between liver fat and diabetes complications. This could influence treatment decisions and improve patient outcomes.
Effectiveness of both therapies remains unclear due to non-significant results. The study may have limited generalizability based on the specific population studied. Potential confounding factors were not fully accounted for in the analysis.
Published in
Publication details and source links for this paper.
Muhammad A, Curtiss P, Siham A, et al. Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes. BMJ Open Diabetes Research & Care. 2025;13(2):e004981. doi:10.1136/bmjdrc-2025-004981
Lower liver fat content was observed in subjects receiving initial triple therapy.
Subjects receiving sequential add-on therapy experienced a greater increase in cIMT.
Greater liver fibrosis was observed in subjects receiving sequential add-on therapy.
Mean HbA1c was 5.7% vs 6.0% in the respective groups, p=NS.
Evidence network
Understand where this research contributes within the broader evidence network.
This study contributes evidence to Metformin, Sequential addition of metformin followed by glipizide and insulin glargine and Carotid intima-media thickness (cIMT), Liver fat content, HbA1c, and 1 more.
This study contributes evidence to
Primary intervention
Metformin
Primary outcomes
Evidence topics
Primary intervention
Primary outcomes
Intervention and outcome relationships this study adds to the evidence network.
Editorial context
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Evidence network role
This section describes how the study fits into the current evidence network. It does not determine whether an intervention works on its own.
2
Related topics
4
Evidence pairs
195
Related studies
Evidence topic
Contributes evidence
Evidence topic
Contributes evidence
Core evidence
The primary outcomes reported in this study.
Metformin → Carotid intima-media thickness (cIMT)
Metformin → Carotid intima-media thickness (cIMT)
Sequential addition of metformin followed by glipizide and insulin glargine → HbA1c
Sequential addition of metformin followed by glipizide and insulin glargine → HbA1c
Sequential addition of metformin followed by glipizide and insulin glargine → Liver fibrosis
Sequential addition of metformin followed by glipizide and insulin glargine → Liver fibrosis
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Relationships organized using the Dediabetes Evidence Intelligence™ framework.
This study contributes to evidence on Metformin Therapies and HbA1c, Metformin Therapies and Carotid intima-media thickness (cIMT).
This study contributes to the evidence on the following intervention-outcome relationships.
Medications
Curated evidence collections and hubs this study is part of.
All studies measuring HbA1c
Measures HbA1c as a key outcome.
All studies on Metformin Therapies
Contributes to Metformin Therapies evidence base.
All studies measuring Carotid intima-media thickness (cIMT)
Measures Carotid intima-media thickness (cIMT) as a key outcome.
Latest published studies
Published within the last 2 years.
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7 results
1 results
7 results
7 results
1 results
Generated from the study's connected evidence using Evidence Intelligence™.
Metformin appears to improve Carotid intima-media thickness (cIMT).
ConsistencyScore™: Consistency cannot yet be determined from the available evidence.
Ranked evidence signals
Carotid intima-media thickness (cIMT)
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | strong positive | ConsistencyScore™ Unclear | 1 study
Why this answer: This answer is based on a single supporting study.
Limitations
Metformin appears to improve Liver fat content.
ConsistencyScore™: Consistency cannot yet be determined from the available evidence.
Ranked evidence signals
Liver fat content
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | strong positive | ConsistencyScore™ Unclear | 1 study
Why this answer: This answer is based on a single supporting study.
Limitations
Sequential addition of metformin followed by glipizide and insulin glargine appears to improve Liver fibrosis.
ConsistencyScore™: Consistency cannot yet be determined from the available evidence.
Ranked evidence signals
Liver fibrosis
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | strong positive | ConsistencyScore™ Unclear | 1 study
Why this answer: This answer is based on a single supporting study.
Limitations
Current evidence does not show a clear benefit of Sequential addition of metformin followed by glipizide and insulin glargine for HbA1c.
ConsistencyScore™: Consistency cannot yet be determined from the available evidence.
Ranked evidence signals
HbA1c
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | neutral | ConsistencyScore™ Unclear | 1 study
Why this answer: This answer is based on a single supporting study.
Limitations
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