Metformin-insulin versus metformin-sulfonylurea combination therapies in type 2 diabetes: a comparative study of glycemic control and risk of cardiovascular diseases in Addis Ababa, Ethiopia
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Date
2020-09
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Addis Abeba University
Abstract
Background: The benefits of combination therapies in the management of type 2 diabetes are
well-documented, while the comparative glycemic control and cardiovascular outcomes among
the different combination options have not been studied well. The study aimed to compare
glycemic control and risk of cardiovascular outcomes of metformin-insulin versus metforminsulfonylurea
combination
therapies
in
type
2 diabetes
mellitus.
Method: A comparative cross-sectional study was conducted in five tertiary level hospitals in
Addis Ababa, Ethiopia. About 321 patients with type 2 diabetes mellitus who were on
continuous treatment follow up on either metformin-insulin or metformin-sulfonylurea
combination therapy were enrolled. Participants were interviewed and their medical records were
reviewed to investigate medication efficacy, safety, and adherence. The primary outcome
measure was glycemic control (reduction in glycated hemoglobin A1c) and the secondary
outcome measures were composite cardiovascular outcomes (myocardial infarction, stroke, heart
failure), microvascular complications (diabetic neuropathy, retinopathy, and nephropathy),
treatment-emergent adverse events, changes in bodyweight, fasting blood sugar, systolic blood
pressure, diastolic blood pressure and lipid profiles (low-density lipoprotein-cholesterol, highdensity
lipoprotein-cholesterol,
and triglycerides).
Results: Of the total participants enrolled, 162 (50.5%) were those who received metformininsulin
and 159 (49.5%) metformin-sulfonylurea combination therapies for a median of 48
months follow-up. Reduction of HbA1c was not different between the two groups, p = .912, with
mean ± SD of -1.04 ± .96 % versus -1.02 ± 1.03%, respectively. Patients who received
metformin-sulfonylurea are 4.3 times more likely to have achieved target HbA1c level compared
to those who received metformin-insulin, p < .001 (AOR=4.31 [95% CI 1.79-10.32]). Risk of
composite cardiovascular outcomes was higher in metformin-insulin group (40.5% versus
34.0%), p = .021. Co-morbidities, body mass index, systolic blood pressure, and HbA1c had a
significant association with composite cardiovascular outcomes. Reductions of bodyweight, lipid
profiles, and microvascular complications were different between the two groups, p < .05.
Conclusion: High proportion of patients who received metformin-sulfonylurea achieved target
HbA1c level and had less composite cardiovascular outcomes compared to those who received metformin-insulin. However, these findings have to be confirmed with randomized control trials
to determine risks associated with insulin use, while efficacy is maintained as second-line
treatment in patients with type 2 diabetes mellitus.
Description
Keywords
Glycemic control, Cardiovascular diseases, Type 2 diabetes mellitus, Metformin, Insulin, Sulfonylurea, Glycated hemoglobin A1c (HbA1c)