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, 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

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.

Conflict of interest statement

Competing Interests: Søren S. Lund, Lise Tarnow, Anne Sofie Astrup, Peter Hovind, Peter K. Jacobsen, Amra Ciric Alibegovic, Ida Parving, Lotte Pietraszek, Merete Frandsen, Peter Rossing, Hans-Henrik Parving and Allan Vaag have reported equity in Novo Nordisk A/S. Lise Tarnow, Hans-Henrik Parving and Allan A. Vaag has received funds from Novo Nordisk A/S for research. Søren S. Lund and Allan A. Vaag have received fees from Novo Nordisk A/S for speaking and Allan A.Vaag has received fees from Novo Nordisk A/S for organising education. All authors are present or former employees at Steno Diabetes Center, Gentofte, Denmark. Steno Diabetes Center is an independent academic institution owned by Novo Nordisk A/S and The Novo Nordisk Foundation.

Figures

Figure 1. Patient flow scheme.
Figure 1. Patient flow scheme.

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Source: PubMed

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