Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study

Søren Søgaard Lund; Lise Tarnow; Anne Sofie Astrup; Peter Hovind; Peter Karl Jacobsen; Amra Ciric Alibegovic; Ida Parving; Lotte Pietraszek; Merete Frandsen; Peter Rossing; Hans-Henrik Parving; Allan Arthur Vaag

doi:10.1371/journal.pone.0003363

Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study

Søren Søgaard Lund, Lise Tarnow, Anne Sofie Astrup, Peter Hovind, Peter Karl Jacobsen, Amra Ciric Alibegovic, Ida Parving, Lotte Pietraszek, Merete Frandsen, Peter Rossing, Hans-Henrik Parving, Allan Arthur Vaag

75 Citations (Scopus)

Abstract

BACKGROUND: Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.

METHODOLOGY/PRINCIPAL FINDINGS: One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.

CONCLUSIONS/SIGNIFICANCE: In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00118937.

Original language	English
Journal	P L o S One
Volume	3
Issue number	10
Pages (from-to)	e3363
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0003363
Publication status	Published - 9 Oct 2008

Keywords

Adult
Blood Glucose
Body Weight
Diabetes Mellitus, Type 1
Female
Hemoglobin A, Glycosylated
Humans
Hypoglycemic Agents
Insulin
Male
Metformin
Middle Aged
Treatment Outcome

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Lund, S. S., Tarnow, L., Astrup, A. S., Hovind, P., Jacobsen, P. K., Alibegovic, A. C., Parving, I., Pietraszek, L., Frandsen, M., Rossing, P., Parving, H.-H., & Vaag, A. A. (2008). Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. P L o S One, 3(10), e3363. https://doi.org/10.1371/journal.pone.0003363

Lund, SS, Tarnow, L, Astrup, AS, Hovind, P , Jacobsen, PK, Alibegovic, AC, Parving, I, Pietraszek, L, Frandsen, M, Rossing, P , Parving, H-H & Vaag, AA 2008, 'Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study', P L o S One, vol. 3, no. 10, pp. e3363. https://doi.org/10.1371/journal.pone.0003363

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title = "Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study",

abstract = "BACKGROUND: Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.METHODOLOGY/PRINCIPAL FINDINGS: One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.CONCLUSIONS/SIGNIFICANCE: In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.TRIAL REGISTRATION: ClinicalTrials.gov NCT00118937.",

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T1 - Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study

AU - Lund, Søren Søgaard

AU - Tarnow, Lise

AU - Astrup, Anne Sofie

AU - Hovind, Peter

AU - Jacobsen, Peter Karl

AU - Alibegovic, Amra Ciric

AU - Parving, Ida

AU - Pietraszek, Lotte

AU - Frandsen, Merete

AU - Rossing, Peter

AU - Parving, Hans-Henrik

AU - Vaag, Allan Arthur

PY - 2008/10/9

Y1 - 2008/10/9

N2 - BACKGROUND: Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.METHODOLOGY/PRINCIPAL FINDINGS: One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.CONCLUSIONS/SIGNIFICANCE: In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.TRIAL REGISTRATION: ClinicalTrials.gov NCT00118937.

AB - BACKGROUND: Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.METHODOLOGY/PRINCIPAL FINDINGS: One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.CONCLUSIONS/SIGNIFICANCE: In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.TRIAL REGISTRATION: ClinicalTrials.gov NCT00118937.

KW - Adult

KW - Blood Glucose

KW - Body Weight

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Hemoglobin A, Glycosylated

KW - Humans

KW - Hypoglycemic Agents

KW - Insulin

KW - Male

KW - Metformin

KW - Middle Aged

KW - Treatment Outcome

U2 - 10.1371/journal.pone.0003363

DO - 10.1371/journal.pone.0003363

M3 - Journal article

C2 - 18852875

SN - 1932-6203

VL - 3

SP - e3363

JO - P L o S One

JF - P L o S One

IS - 10

ER -

Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study

Abstract

Keywords

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