Exp Clin Endocrinol Diabetes 2018; 126(07): 460-464
DOI: 10.1055/s-0043-113830
Article
© Georg Thieme Verlag KG Stuttgart · New York

Safety of Metformin Therapy in Patients with Type 2 Diabetes Living on an Oxygen-Deficient Plateau, Tibet, China

Xuemei Lv
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
Qian Ren
2   Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, P. R. China
,
Lingli Zhou
2   Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, P. R. China
,
Yanyan Geng
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
Jia Song
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
A Mina
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
Basang Puchi
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
Senlin Yang
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
Shuyou Meng
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
,
Lihui Yang
1   Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Tibet, P. R. China
› Author Affiliations
Further Information

Publication History

received 20 March 2017
revised 24 May 2017

accepted 19 June 2017

Publication Date:
08 November 2017 (online)

Abstract

Background In the general population, the absolute risk of lactic acidosis in patients treated with metformin appears to be low. However, in the Tibetan plateau, an extreme oxygen-deficient environment, there are no data available concerning the safety of metformin. The aim of our study is to assess the safety of metformin in people of the plateau area.

Methods We conducted an observational cross-sectional study in Tibet. All the 166 subjects were divided into two groups: T2DM+metformin group and T2DM group. Clinical characteristics as well as lactate levels were measured in all subjects. The association between lactate, metformin use, FBG, HbA1c, eGFR, and other potential predictors was evaluated.

Results A total of 166 subjects were enrolled in this study. Average age was 51.7±12.3 years, and the percentage of male participants was 67%. The median level of lactate was 1.89 (1.35–2.91) mmol/L in all the subjects. The mean (±SD) lactate concentration in patients treated with metformin, versus those who were not, was 2.35±1.42 vs 2.29±1.65 mmol/L, respectively (mean difference 0.06 mmol/L, 95% CI: −0.48–0.60, P=0.556). FBG was significantly higher in the high lactate group than in the low lactate group (12.1±4.1 vs. 10.5±4.0 mmol/L, P=0.018). Similarly, HbA1c level was also significantly higher in the high lactate group than in the low lactate group (12.3±2.6 vs. 11.0±3.0%, P=0.008).

Conclusions In the oxygen-deficient Tibetan plateau, lactate concentration among patients on metformin was not significantly different from patients without metformin. The level of lactate was significantly associated with FBG and HbA1c levels.

Supplementary Material

 
  • References

  • 1 UK Prospective Diabetes Study (UKPDS) Group . Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865
  • 2 American Diabetes Association . Standards of medical care in diabetes—2017. Diabetes Care 2017; 40: S1-S135
  • 3 Inzucchi SE, Bergenstal RM. et al. Management of hyperglycemia in type 2 diabetes: a patient-centered ap- proach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35: 1364-1379
  • 4 China Diabetes Society . China guideline for type 2 diabetes. 2013. Peking University Medical Publisher; Peking: 2013
  • 5 Stang M, Wysowski DK, Butler-Jones D. Incidence of lactic acidosis in metformin users. Diabetes Care 1999; 22: 925-927
  • 6 Seheult J, Fitzpatrick G, Boran G. Lactic acidosis: An update. Clin Chem Lab 2017; 55: 322-333
  • 7 Stacpoole PW, Wright EC, Baumgartner TG. et al. Natural history and course of acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group. Am J Med 1994; 97: 47-54
  • 8 Ferrannini E. The target of metformin in type 2 diabetes. N Engl J Med 2014; 371: 1547-1548
  • 9 Kajbaf F, Lalau JD. Mortality rate in so-called “metformin-associated lactic acidosis”: a review of the data since the 1960s. Pharmacoepidemiol Drug Saf 2014; 23: 1123-1127
  • 10 Eppenga WL, Lalmohamed A, Geerts AF. et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: A population-based cohort study. Diabetes Care 2014; 37: 2218-2224
  • 11 Sipahi S, Solak Y, Acikgoz S. et al. Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease. Int Urol Nephrol 2016; 48: 1305-1312
  • 12 Cryer DR, Nicholas SP, Henry DH. et al. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care 2005; 28: 539-543
  • 13 Bodmer M, Meier C, Krahenbuhl S. et al. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care 2008; 31: 2086-2091
  • 14 Hitchings AW, Archer JR, Srivastava SA. et al. Safety of metformin in patients with chronic obstructive pulmonary disease and type 2 diabetes mellitus. COPD 2015; 12: 126-131
  • 15 Yang Y, Zhou R, Yan Y. et al. Seasonal variations and size distributions of water-soluble ions of atmospheric particulate matter at Shigatse, Tibetan Plateau. Chemosphere 2016; 145: 560-567
  • 16 Beall CM, Strohl KP, Blangero J. et al. Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives. Am J Phys Anthropol 1997; 104: 427-447
  • 17 Ma L, Chen Y, Jin G. et al. Vascular endothelial growth factor as a prognostic parameter in subjects with "Plateau Red Face". High Alt Med Biol 2015; 16: 147-153
  • 18 Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574-579
  • 19 Levey AS, Stevens LA, Schmid CH. et al. A new equation to estimate glomerular filtration rate. Am Intern Med 2009; 150: 604-612
  • 20 Chandra SP, Vinay N, Bhawna B. Determination of lactic acid with special emphasis on biosensing methods: A review. Biosensors and Bioelectronics 2016; 86: 777-790
  • 21 DiMauro FM, Schoeffler GL. Point of Care Measurement of Lactate. Top Companion Anim Med 2016; 31: 35-43
  • 22 LIm VC, Sum CF, Chan ES. et al. Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal function. Int J Clin Pract 2007; 61: 1829-1833
  • 23 Scale T, Harvey JN. Diabetes, metformin and lactic acidosis. Clinical Endocrinology 2011; 74: 191-196
  • 24 Lin YC, Lin LY, Wang HF. et al. Fasting plasma lactate concentrations in ambulatory elderly patients with type 2 diabetes receiving metformin therapy: A retrospective cross-sectional study. J Clin Med Assoc 2010; 73: 617-622
  • 25 Mongraw-Chaffin ML, Matsushita K, Brancati FL. et al. Diabetes medication use and blood lactate level among participants with type 2 diabetes: The atherosclerosis risk in communities carotid MRI study. Plos One 2012; 7: e51237
  • 26 Davis TM, Jackson D, Davis WA. et al. The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The fremantle diabetes Study. Br J Clin Pharmacol 2001; 52: 137-144
  • 27 Li L, Jick S, Gopalakrishnan C. et al. Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: A cohort study in Denmark and the UK. Diabet Med 2017; 34: 485-489