Metformin and Pioglitazone: Actions and uses




Mechanism of action:

  • Thiazolidinediones, such as pioglitazone, are synthetic ligands for peroxisome proliferator-activated receptors (PPARs).
  • PPARs are particularly found in skeletal muscles, adipose tissue, liver, etc.
  • the role of PPAR is to alter the transcription of genes influencing carbohydrate and lipid metabolism, resulting in changed amounts of protein synthesis and, therefore, metabolic changes.
  • Pioglitazone improves glycaemic control in people with Type 2 diabetes by improving insulin sensitivity through its action at PPAR gamma 1 and PPAR gamma 2 and affects lipid metabolism through action at PPAR alpha.
  • Together, these can increase glucose uptake and utilization in the peripheral organs and decrease gluconeogenesis in the liver, thereby reducing insulin resistance.

Metformin and Pioglitazone


1.Type 2 Diabetes- At the moment, the most insulin-resistant patients—identifiable by increased waist circumference, low HDL cholesterol level, and fatty liver and patients with a high risk of CVD are likely to benefit from pioglitazone.

2.Possible use in lichen planopilaris – under research(for hair growth)

Side effects:

  1. Weight gain
  2. CHF
  3. Bone fractures
  4. Macular edema
  5. Possibly bladder cancer but the association is not yet proven.
  6. Allergic reactions



Mechanism of action

  • Metformin reduces serum glucose levels by several different mechanisms, notably through nonpancreatic mechanisms without increasing insulin secretion.
  • It increases the effects of insulin; hence, it is termed “insulin sensitizer”.
  • Metformin also suppresses endogenous glucose production by the liver, which is mainly due to a reduction in the rate of gluconeogenesis and a small effect on glycogenolysis.
  • Moreover, metformin activates the enzyme adenosine monophosphate kinase (AMPK) resulting in the inhibition of key enzymes involved in gluconeogenesis and glycogen synthesis.
  • AMPK regulates the cellular and organ metabolism and any decrease in hepatic energy leads to the activation of AMPK.


Diabetes mellitus

  1. Metformin is primarily used for the treatment of type 2 diabetes mellitus, particularly in obese patients.
  2. Pre-diabetes
  3. Gestational diabetes
  4. Polycystic ovary syndrome
  5. Cancer protection -A large case-control study has suggested that metformin might protect patients against pancreatic cancer. Metformin has shown strong antiproliferative effects on colon, pancreatic, breast, ovarian, prostate and lung cancer cells. This may be related to its antioxidant effect.
  1. HIV-associated diabetes: The use of some of the antiretroviral drugs in HIV-infection has been associated with glucose tolerance, insulin resistance, hyperinsulinemia and type 2 diabetes mellitus. Metformin has been shown to reduce visceral adiposity and insulin resistance after 8 weeks.
  1. Nephrotoxicity prevention

Recent studies have suggested that metformin may have therapeutic or renoprotective effects against nephrotoxic agents. It has also been shown to have good efficacy in diabetic nephropathy.

Side effects

Metformin has no significant adverse effects;

1.Lactic acidosis with the following symptoms: Dizziness, severe drowsiness, muscle pain, tiredness, chills, blue/cold skin, fast/difficult breathing, slow/irregular heartbeat, stomach pain with diarrhea, nausea or vomiting.

2.Hypoglycemia in case if it is used in combination with other drugs. Metformin usually does not cause hypoglycemia; however, low blood sugar may occur if this drug is used with other anti-diabetic drugs.

3. A serious allergic reaction to this drug is rare.

4. Gastrointestinal intolerance is one of the most frequently occurred adverse effects.

How is Pioglitazone different from Metformin:          

1. The major action of Metformin is sensitizing liver cells to insulin whereas pioglitazone sensitizes the peripheral organs and skeletal muscles

2. Metformin has other uses apart from the treatment of Diabetes Mellitus whereas pioglitazone has limited usage.

3. The mechanism of action is different for both. But both can be used in combination therapy to achieve optimal glycemic control.

4. Correction of dyslipidemia can be achieved in pioglitazone which is not the case with Metformin.

5. Metformin reduces macro and microvasculature complications which is not observed with Pioglitazone.

6. In the case of Metformin resistance, Pioglitazone has been proved successful.


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