Oral Hypoglycaemics

Class Biguanides Sulfonylureas Glitazones Gliflozins
Example Metformin Gliclazide Pioglitazone Dapagliflozin
Uses T2DM T2DM T2DM T2DM
Mechanism of Action Delay glucose absorption, increase peripheral insulin sensitivity, inhibit hepatic gluconeogenesis Increase insulin secretion from pancreatic β-cells. May increase insulin sensitivity Activates the intranucleic PPARγ receptor, affecting gene translation and increasing insulin sensitivity Inhibits glucose reabsorption by the S-GLUT2 co-transporter in the kidney, increasing glucose elimination in urine
Dosing 500mg-2g BD 40-160mg BD 15-30mg daily 5-10mg daily
Absorption Bioavailability 60% Bioavailability 80% High bioavailability. Delayed onset and late peak effect given MoA Bioavailability > 75%
Distribution Minimally protein bound Extensively bound to albumin by non-ionic forces, such that they do not tend to displace other highly protein bound drugs Low VD (0.6L.kg-1)
Metabolism Not metabolised Partial hepatic to inactive metabolites Extensive hepatic phase I to inactive and active metabolites Extensive hepatic to inactive metabolites
Elimination Renal elimination of active drug Renal elimination of active drug and inactive metabolites Renal and GI elimination of active and inactive metabolites Renal of inactive drug
CVS May precipitate fluid retention
Renal Contraindicated in renal impairment due to increased risk of lactic acidosis Containdicated in renal impairment (< 60ml.min-1) as it has no benefit
MSK Photosensitivity
Metabolic ↑ Appetite, weight gain. Hypoglycaemia in fasting. Weight loss, reduced insulin requirements
Renal Increased UTI and thrush risk
GIT Nausea, Diarrhoea Cholestasis
Toxic Severe lactic acidosis secondary to inhibition of oxidative glucose metabolism, especially in renal failure and alcoholics Cross placenta, causing foetal hypoglycaemia.

References

  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  3. Dapaglifozin for Type 2 Diabetes. 2013. Aust Prescr 2013;36:174-9.
  4. Kilov G, Leow S, Thomas M. SGLT2 inhibition with dapagliflozin: A novel approach for the management of type 2 diabetes. American Family Physician. Volume 42, No.10, October 2013 Pages 706-710.
Last updated 2017-09-21

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