Oral Glucose Lowering Agents (OGLAs)

Oral Glucose Lowering Agents (OGLAs)

Class	Example
Biguanides	Metofrmin
SGLT-2 inhibitors	Canagliflozin, empagliflozin, dapagliflozin
GLP-1 agonists	Exenatide, liraglutide, semaglutide
DPP-4 inhibitors	Sitagliptin, linagliptin
Sulfonylureas	Glipizide, gliburide, chlorpropamide
Thiazolidinediones	Pioglitazone, rosiglitazone

Prescribing OGLAs

• Patients who can tolerate metformin
  • HbA1C <7.5%:
    • Metformin
  • HbA1C > 7.5%:
    • Metformin + Sulfonylurea
    • Metformin + DPP-4 inhibitor
    • Metformin + Thiazolidinedione
    • Metformin + SGLT-2 inhibitor
  • Persistent HbA1C >7.5%: Metformin +
    • Metformin + DPP-4 inhibitor + Sulfonylurea
    • Metformin + Thizolidedinedione + Sulfonylurea
    • Metformin + Sulfonylurea + SGLT-2 inhibitor
    • Metformin + Thiazolidedinedione + SGLT-2 inhibitor
    • Insulin therapy

Metformin

Metformin is a biguanide. It is one of the cornerstones of pharmacotherapy for T2DM along with exercise and diet. It has a number of actions which improve glucose tolerance. Unlike sulphonylureas, metformin does not cause hypoglycaemia or weight gain and is therefore preferred as first-line, particularly in overweight patients.

Mechanism of action: complex.

Inhibits hepatic gluconeogenesis

Increases insulin sensitivity

Reduces gastrointestinal absorption of carbohydrates

• Indications
  • Type 2 diabetes
  • Polycystic ovarian syndrome
  • Non-alcoholic fatty liver disease
• Contraindications
  • Chronic kidney disease
    • Review dose if creatinine is > 130 umol/L (eGFR < 45 ml/min)
    • Stop if creatinine is > 150 umol/L (eGFR < 30 ml/min)
  • Advanced cirrhosis
  • Lung diseae
  • States of tissue hypoxia e..g myocardial infarction, sepsis, acute kidney injury and severe dehydration
  • Iodine-containig contrast media (angiography, pyelography) since these can provoke renal impairment duet to contrast nephropathy
    • Stop metformin on the day of the procedure and continue 48 hours after
  • Alcohol abuse (relative contraindication)
• Adverse effects
  • Lactic acidosis
  • Gastrointestinal upset i.e. nausea, anorexia, diarrhoea (intolerable in 20% of patients)

GLP-1 agonists

GLP-1 agonists are commonly used as an adjunct to metformin or as an alternative. They are given as a SC injection (except semaglutide). They are very expensive and have been approved for weight loss (an attractive choice for obese patients). They have few but severe adverse effects.

• Indications
  • BMI > 35 with specific psychological or medical condition associated with obesity
  • BMI < 35 for whom insulin therapy would have significant occupational implications
• Contraindications
  • MEN-2 syndrome
  • Personal history or family history of medullary thyroid cancer
• Adverse effects
  • Acute pancreatitis

DPP-4 inhibitors

DPP-4 inhibitors are ommonly used as adjuncts to metformin or as alternatives. It has a similar mechanism to GLP-1 agonists but is weight-neutral. They have very few adverse effects (including nausea and vomiting)

Sulfonylureas

Sulfonylureas have fallen out of favor (due to weight gain and hypoglycemia). They still may be an appropriate monotherapy for patients in whom metformin is contraindicated.

MOA: Increases insulin release

• Adverse effects
  • Weight gain
  • Hypoglycemia (especially with long-acting preparations)
  • Rare side effects
    • SIADH
    • Bone marrow suppression
    • Cholestasis
    • Peripheral neuropathy
• Contraindications
  • Pregnancy
  • Breastfeeding

Thiazolidinediones

Thiazolidinediones have fallen out of favor due to their propensity to cause water retention. They still may be an appropriate monotherapy for patients in whom metformin is contraindicated.

MOA: Increase peripheral insulin sensitivity. Weight-neutral.

• Contraindications
  • Congestive heart failure
• Adverse effects
  • Liver disturbances (monitor LFTs)
  • Water retention (edema)
  • Weight gain
  • Increased risk of fractures
  • Increased risk of bladder cancer (hazard ration 2.64)