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


RESULTS
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
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.


BACKGROUND
ClinicalTrials.gov NCT00118937.
Steno Diabetes Center, Gentofte, Denmark. sqrl@steno.dk
Søren Søgaard
SS
Lund
Lise
L
Tarnow
Anne Sofie
AS
Astrup
Peter
P
Hovind
Peter Karl
PK
Jacobsen
Amra Ciric
AC
Alibegovic
Ida
I
Parving
Lotte
L
Pietraszek
Merete
M
Frandsen
Peter
P
Rossing
Hans-Henrik
HH
Parving
Allan Arthur
AA
Vaag
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin