Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar;33(3):501-6.
doi: 10.2337/dc09-1749. Epub 2009 Dec 29.

Secondary failure of metformin monotherapy in clinical practice

Affiliations

Secondary failure of metformin monotherapy in clinical practice

Jonathan B Brown et al. Diabetes Care. 2010 Mar.

Abstract

OBJECTIVE We sought to document the secondary failure rate of metformin monotherapy in a clinical practice setting and to explore factors that predict therapeutic failure. RESEARCH DESIGN AND METHODS We studied 1,799 type 2 diabetic patients who, between 2004 and 2006, lowered their A1C to <7% after initiating metformin monotherapy as their first-ever anti-hyperglycemic drug. We examined all A1C values recorded through 31 December 2008 (2-5 years of follow-up), defining secondary failure as a subsequent A1C > or =7.5% or the addition or substitution of another anti-hyperglycemic agent. We used logistic regression to identify factors associated with the probability of secondary failure. RESULTS Of the 1,799 patients studied, 42% (n = 748) experienced secondary failure; the mean failure rate was 17% per year. However, patients who initiated metformin within 3 months of diabetes diagnosis failed at an age-and A1C-adjusted rate of 12.2% (10.5-14.4%) per year, and patients who initiated while A1C was <7% failed at an adjusted rate of 12.3% per year. An interaction term between duration of diagnosed diabetes and A1C was not significant. Age, duration, and A1C at initiation were the only factors that predicted secondary failure. CONCLUSIONS Although metformin failure may occur more rapidly in clinical practice than in clinical trails, initiating it soon after diabetes diagnosis and while A1C is low might preserve beta-cell function, prolong the effectiveness of metformin, reduce lifetime glycemic burden, and prevent diabetes complications. Our findings support the current treatment algorithm for hyperglycemia management that recommends metformin initiation when diabetes is first diagnosed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Kaplan-Meier plot of secondary failure of metformin monotherapy by categories of duration of diabetes at metformin initiation adjusted for age and A1C at initiation and the percent per year (95% CIs) experiencing secondary failure.
Figure 2
Figure 2
Kaplan-Meier plot of secondary failure of metformin monotherapy by categories of A1C at metformin initiation adjusted for age and diabetes duration at initiation and the percent per year (95% CIs) experiencing secondary failure.

Similar articles

Cited by

References

    1. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM: Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403 - PMC - PubMed
    1. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M: Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–1350 - PubMed
    1. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V: Indian Diabetes Prevention Programme (IDPP). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006;49:289–297 - PubMed
    1. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B: American Diabetes Association, European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193–203 - PMC - PubMed
    1. Nichols GA, Alexander CM, Girman CJ, Kamal-Bahl SJ, Brown JB: Treatment escalation and rise in HbA1c following successful initial metformin therapy. Diabetes Care 2006;29:504–509 - PubMed

Publication types