Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial
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OBJECTIVES: To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes. DESIGN: Randomised, double blind, double dummy, parallel trial. SETTING: Secondary care in Denmark between 2003 and 2006. PARTICIPANTS: Non-obese patients (BMI </=27) with preserved beta cell function. INTERVENTIONS: After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA(1c)) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA(1c) concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached. MAIN OUTCOME MEASURE: HbA(1c) concentration. RESULTS: Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA(1c) concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA(1c) 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments -2.51 kg, 95% confidence interval -4.07 to -0.95). CONCLUSIONS: In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide. TRIAL REGISTRATION: NCT00118963.
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Metformin added to insulin-based regimens improves glycemic control, limits changes in body weight, reduces hypoglycemia incidence, and reduces insulin requirements, allowing a 15-25% reduction in total insulin dosage.
“Metformin as added to insulin-based regimens has been shown to improve glycemic control, limit changes in body weight, reduce hypoglycemia incidence, and to reduce insulin requirements (sparing effect), allowing a 15–25% reduction in total insulin dosage [28,29].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [29]
Metformin may limit or decrease the weight gain experienced with sulfonylureas, TDZ, insulin, HAART, and antipsychotic drugs.
“or may limit or decrease the weight gain experienced with sulfonylureas [18], TDZ [104], insulin [29,75], HAART [97], and antipsychotics drugs [94].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [29]
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- Authors
- Lund, S. S., Tarnow, L., Frandsen, M., Nielsen, B. B., Hansen, B. V., Pedersen, O., Parving, H.-H., & Vaag, A. A.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- University of Copenhagen (DK)
- Lund University (SE)
- Corresponding author
- Lund, S. S
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2009-11-09
- Volume
- 339
- Issue
- nov09 1
- Pages
- b4324-b4324
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC2775102
- OpenAlex
- W1976422603
- Cited by
- 41
- References
- 60
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 6 · 2012: 3
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, insulin therapy, metformin, repaglinide, insulin secretagogues, non-obese patients, glycemic control, HbA1c, biphasic insulin aspart, hypoglycemia, weight gain, beta-cell function, combination therapy
- MeSH terms
- Blood Glucose, Carbamates, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Metformin, Middle Aged, Patient Compliance, Piperidines, Weight Gain, Treatment Outcome, Insulin Aspart
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