Metformin and Pioglitazone

Metformin and Pioglitazone Brand Names- Actoplus Met | Actoplus Met XR

What is Metformin and Pioglitazone

Metformin and pioglitazone is a combination product containing 2 antidiabetic agents. The product is used as an adjunct to diet and exercise, to lower blood glucose levels in adults with type 2 diabetes mellitus (DM).

Metformin is a biguanide agent that improves insulin sensitivity. While metformin carries a low risk for lactic acidosis as outlined in the prescribing information and boxed warning of all metformin-containing products, care in prescribing and monitoring can reduce this risk.

Pioglitazone is a member of the thiazolidinedione (TZD) class. Pioglitazone has been shown to reduce some cardiovascular endpoints, but without conclusive evidence of benefit.

The TZDs, including pioglitazone, cause or exacerbate congestive heart failure in some patients and are contraindicated in those with established NYHA Class III or IV heart failure.

Metformin is first-line in the treatment of type 2 DM. In patients with established cardiovascular (CV) disease, HF, or chronic kidney disease (CKD), a sodium-glucose co-transporter 2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1 RA) with proven CV benefit and reduction of CKD progression is recommended for add-on therapy, independent of baseline A1C or individualized A1C target.

In patients without indicators of high-risk or established CVD, HF, or CKD, pioglitazone and other TZDs are a therapeutic option associated with glycemic durability; however, the benefits must be balanced with the risk of adverse effects such as heart failure, edema, reduced bone mineral density, and weight gain.

In patients who are starting on insulin therapy and are taking pioglitazone, discontinue or reduce the dose of pioglitazone.

Hypoglycemia, fluid retention, and edema are most common when pioglitazone is used in combination with insulin. Pioglitazone may be used with insulin as long as the insulin dose is carefully titrated to glycemic response.

Although not FDA-approved, the TZDs and metformin may prevent future development of diabetes in 60% to 75% and 25% to 30% of subjects with prediabetes, respectively

Indications

  • type 2 diabetes mellitus

For the treatment of type 2 diabetes mellitus not controlled by diet and exercise

for use when either metformin or pioglitazone alone is inadequate

Side Effects

  1. abdominal pain
  2. anemia
  3. anorexia
  4. blurred vision
  5. bone fractures
  6. cholestasis
  7. diarrhea
  8. dizziness
  9. dysgeusia
  10. dyspepsia
  11. dyspnea
  12. edema
  13. elevated hepatic enzymes
  14. flatulence
  15. fluid retention
  16. folate deficiency
  17. headache
  18. heart failure
  19. hepatic encephalopathy
  20. hepatic failure
  21. hepatitis
  22. hyperbilirubinemia
  23. hypoglycemia
  24. infection
  25. jaundice
  26. lactic acidosis
  27. macular edema
  28. malaise
  29. megaloblastic anemia
  30. menstrual irregularity
  31. metabolic acidosis
  32. metallic taste
  33. myalgia
  34. nausea
  35. new primary malignancy
  36. osteopenia
  37. peripheral edema
  38. pharyngitis
  39. rhabdomyolysis
  40. sinusitis
  41. visual impairment
  42. vitamin B12 deficiency
  43. weight gain

Monitoring Parameters

  • blood glucose
  • CBC
  • glycosylated hemoglobin A1c (HbA1c)
  • LFTs
  • serum bilirubin
  • serum creatinine/BUN
  • weight

Contraindications

  • acidemia
  • acute heart failure
  • acute myocardial infarction
  • adrenal insufficiency
  • alcoholism
  • anemia
  • bladder cancer
  • bone fractures
  • breast-feeding
  • burns
  • cardiac disease
  • cardiogenic shock
  • children
  • contraception requirements
  • dehydration
  • diabetic ketoacidosis
  • diarrhea
  • edema
  • ethanol ingestion
  • ethanol intoxication
  • fever
  • gastroparesis
  • geriatric
  • GI obstruction
  • heart failure
  • hepatic disease
  • hypercortisolism
  • hyperglycemia
  • hyperthyroidism
  • hypoglycemia
  • hypothyroidism
  • hypoxemia
  • ileus
  • infection
  • lactic acidosis
  • malnutrition
  • menstrual irregularity
  • metabolic acidosis
  • new primary malignancy
  • osteoporosis
  • peripheral edema
  • pernicious anemia
  • pituitary insufficiency
  • polycystic ovary syndrome
  • pregnancy
  • pulmonary edema
  • radiographic contrast administration
  • renal disease
  • renal failure
  • renal impairment
  • sepsis
  • surgery
  • trauma
  • type 1 diabetes mellitus
  • vomiting

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