Metformin and its gastrointestinal problems: A review

Abstract

Metformin is a biguanide class of drugs and has been recommended as first-line therapy for type 2 diabetes. It has a good safety profile, efficacy, comparatively reduced cost, and potential cardiovascular benefits. Metformin is an insulin-sensitizing agent, its bioavailability is 50%-60%. Generally, A1C levels are lowered by 1.5% points by metformin monotherapy. Treatment with metformin decreases fasting plasma glucose concentrations by 25% to 30% and decreases the production of glucose. Metformin reduces hepatic glucose production and absorption of glucose in the intestine. In addition to it, decreases fatty acids oxidation. In liver and skeletal muscles the mitochondrial function and AMP Activated Protein Kinase (AMPK) activity are considered as potential mechanisms and has gained much attention by which metformin exerts its advantageous effects. In the gut enteroendocrine cells secret glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are considered as important determinants for the disposal of glucose following a meal. Glucose production is reduced either by decreasing gluconeogenesis or by glycogenolysis. Treatment with metformin is, nevertheless, very often associated with gastrointestinal side effects and quality of life and treatment adherence is negatively affected in patients of type 2 diabetes. The most common gastrointestinal symptoms are diarrhea, heartburn, and nausea, followed by abdominal pain, bloating, and retching. The mechanism lying under gastrointestinal intolerance caused by metformin is unclear. However, there are different hypothesis proposed, including stimulation of intestinal secretion of serotonin, alteration in incretin and metabolism of glucose, and malabsorption of bile salts. Metformin is used clinically in diabetes, polycystic ovary syndrome, and in obese for weight reduction. It has cardioprotective effect and its use is recently being studied in cancer and HIV associated metabolic abnormalities.

Prevalence of cardiovascular autonomic neuropathy and gastroparesis symptoms among patients with type 2 diabetes who attend a primary health care center

“…In this study, we found that metformin use emerged as an independent factor for gastroparesis symptoms in patients with T2DM. However, since The most common gastrointestinal side effects of metformin are diarrhea, nausea, abdominal pain and heartburn which were not frequently encountered in the present study, this might eliminate the possibility of metformin as a cause of GI symptoms in the current study [64–65]. Similar findings were observed by Dickman R. et al [34] regarding metformin use and the risk of gastroparesis symptoms (OR = 1.97, 95% CI = 1.19–3.28, p < 0.05), and they related this relationship to the possibility of a synergistic effect of metformin with gastroparesis to produce more GI symptoms, or the possibility that the presence of post-prandial distress syndrome was a cause of GI symptoms, rather than delayed gastric emptying.…”

The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

“…They are most likely related to high concentration of metformin in the intestine, increased secretion of serotonin from enterochromaffin cells, decreased ileum absorption of the bile acids, increased secretion of GLP-1 from enterocytes and altered microbiome. All these factors have a substantial influence on gastrointestinal regulation, particularly intestinal motility and secretion [ 294 ].…”

“…These findings are of clinical importance because in the younger population vitamin B12 is often associated with gastroparesis, megaloblastic anemia and coeliac disease. At least three putative mechanisms of metformin-induced deficiency of vitamin B12 have been proposed, including: (1) alteration of microbiome resulting in the binding of the intrinsic factor-vitamin B12 complex (IF-vitamin B12 complex) to bacteria and blocking its absorption into circulation, (2) altering the intestinal motility and (3) inhibition of the calcium-dependent IF-vitamin B12 complex binding to the receptor located in the terminal ileum [ 294 ]. The risk of lactic acidosis is described in the section titled “Nephroprotection”.…”

Analisis Kualitas Hidup Pasien Diabetes Melitus Tipe 2 Berdasarkan Pola Peresepan Antidiabetik dan Komplikasi

“…penggunaan insulin dapat mengontrol glukosa darah dengan baik, namun beberapa pasien mengalami efek negatif dari penggunaan insulin yaitu merasa takut, sakit, cemas dan tidak nyaman karena efek samping yang ditimbulkan yaitu hipoglikemia 9 . Selain insulin, terdapat beberapa efek samping antidiabetik oral yang kerap muncul misalnya metformin dapat menyebabkan gangguan gastrointestinal seperti mual, muntah, diare serta asidosis laktat sebesar 20-30% 10 . Akarbose dapat menyebabkan perut kembung dan diare 11 .…”