Metformin hydrochloride

Description

Metformin hydrochloride is an insulin-sensitizing agent used to treat type 2 diabetes. It is increasingly being used with other diseases featuring insulin resistance, like polycystic ovary syndrome and non-alcoholic steatohepatitis. Metformin (MET) exists in various forms: diprotonated (H2MET)2+ in strong acidic solution, monoprotonated (HMET)+ in weak acid, MET in neutral and deprotonated (MET)- in strong alkali solution.

Originator

Diabetex ,Germania

The Uses of Metformin hydrochloride

1,1-Dimethylbiguanide, Hydrochloride is a antihyperglycemic biguanide with diverse biological activities, including the stimulation of AMPK. It is used as an antidiabetic agent, used in polycystic ovary syndrome, non-alcoholic fatty liver disease and diabetes mellitus type 2. It may also reduce weight gain in people taking atypical antipsychotics, used in a study to investigate its role in enhancing the secretions of plasma active glucagon-like peptide-1 (GLP-1) levels.

Definition

ChEBI: A hydrochloride resulting from the reaction of metformin with one molar equivalent of hydrogen chloride.

Manufacturing Process

The boiling mixture of 1,000 L xylene, 450 kg dimethylamine and 840 kg dicyanamide was added 365 kg hydrogene chloride. Yield of biguanide, 1,1- dimethyl-, hydrochloride 1,588 kg (96%). Biguanide, 1,1-dimethyl-, hydrochloride may be recrystallysed from methanol.

brand name

Fortamet (Andrx); Glucophage (Bristol-Myers Squibb); Glumetza (Depomed); Riomet(Ranbaxy).

Biological Activity

Antidiabetic agent; lowers plasma glucose levels and improves insulin sensitivity. Inhibits hepatic gluconeogenesis via activation of the LKB1/AMPK pathway. Displays antiproliferative effects in cancer cell lines.

Biochem/physiol Actions

Metformin is an antidiabetic agent that reduces blood glucose levels and improves insulin sensitivity. Its metabolic effects, including the inhibition of hepatic gluconeogenesis, are mediated at least in part by activation of the LKB1-AMPK (AMP-activated protein kinase) pathway. Activation of this pathway also appears to be involved in the antiproliferative and proapoptotic actions of metformin in cancer cell lines.

Veterinary Drugs and Treatments

Metformin may be useful in the adjunctive treatment of non-insulin dependent diabetes mellitus in cats. Only limited trials of the drug have been performed in cats, with only very limited success when the drug is used alone. Studies comparing its safety and efficacy with other oral antihyperglycemics (e.g., glipizide or insulin) were not located.

Drug interactions

Potentially hazardous interactions with other drugs
Alcohol: increased risk of lactic acidosis.
Cimetidine: inhibits renal excretion of metformin

Metabolism

Metformin is not metabolised to any great extent, and is entirely excreted unchanged in the urine.

References

1) Zhou et al. (2001), Role of AMP-activated protein kinase in mechanism of metformin action; J. Clin. Invest., 108 1167 2) Shaw et al. (2005), The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin; Science, 310 1642 3) Shi et al. (2012), Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy; Cell Death Dis., 3 e275 4) Rego et al. (2017) Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systemic review; Oncol. Lett., 13 554 5) Lee et al. (2017) PGC1α Activators Mitigate Diabetic Tubulopathy by Improving Mitochondrial Dynamics and Quality Control; J. Diabetes Res., 2017 6483572 6) Zheng et al. (2012) Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin; Diabetes, 61 217 7) Katila et al. (2017) Metformin lowers α-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson’s disease; Neuropharmacology, 125 396 8) Coll et al. (2020), GDF15 mediates the effects of metformin on body weight and energy balance; Nature, 578 444