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Diabetes Mellitus: Pharmacotherapy- SGLT, Centrally Acting Dopamine Agonists & Bile Acid Sequestrants!

 PHARMACOTHERAPY:

Medications classifications include:

  1.  Sulfonyl Urea's
  2. Nonsylfonylurea Secretagogues (a-Glinides)
  3. Biguanides
  4. Thiazolidinediones
  5. a-Glucosidase Inhibitors
  6. Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
  7. Sodium-glucose co-transporter (SGLT) Inhibitors 
  8. Central-Acting Dopamine Agonists
  9. Bile Acid Sequestrants
  10. Insulin therapy

7.SODIUM-GLUCOSE CO-TRANPORTER (SGLT-2) INHIBITORS

The drugs approved include Canagliflozin, Dapagliflozin, Empagliflozin.

Mechanism of Action:

  • Glucose is freely filtered buy the kidney glomeruli and is reabsorbed in the proximal convoluted tubules by the action of sodium glucose co-transporters (SGLT). SGLT accounts for 90% of the glucose reabsorption and its inhibition causes glycosuria in people with diabetes, lowering plasma glucose levels.

Dose:

Canagliflozin: 100 & 300mg- 100mg daily if usual dose. 300mg daily can be used if eGFR resulting in lowering HDL. 

Dapagliflozin: 3 & 10mg- 10 mg daily. 3mg daily in hepatic failure.

Empagliflozin: 10 & 25mg- 10mg daily. 25 mg daily can be used if necessary.


8.CENTRAL ACTING DOPAMINE AGONISTS

  • A quick release formulation of a central acting dopamine agonist Bromocriptine was approved by the FDA in May 2009 for the treatment of T2DM.

Mechanism of Action:

  • The exact mechanism of action of how bromocriptine regulates glycemic control is unknown, however, data indicates that bromocriptine administered in the morning improves insulin sensitivity and this is a likely result of its effect on dopamine oscillations.

Clinical use:

  • A modest A1c reduction of 0.1%-0.4% is expected from this drug.

Adverse Effects:

  • Rhinitis
  • Dizziness
  • Asthenia
  • Headache
  • Sinusitis
  • Constipation
  • Nausea

Dose:

  • When used to treat patients with T2DM, bromocriptine should be taken 2hr after waking up in the morning with food. 
  • The initial dose is 0.8mg, titrated up weekly until a maximum dosage of 4.8mg/day is achieved.

Contraindication:

  • It is contraindicated in patients with migraine and in women who are nursing.


9.BILE ACID SEQUESTRANTS

  • Colesevelam is the only bile acid sequestrant currently approved as the adjunctive therapy to improve glycemic control in conjunction with diet, exercise and insulin or oral agents for the treatment of T2 DM.

Mechanism of action:

It acts on the intestinal lumen to bind bile acid but whether this is the drugs only action that results in plasma glucose lowering or if a secondary systemic effect to bile acid binding is unknown.

Clinical use:

  • An A1c reduction of approximately 0.4% can be expected when added to metformin, sulfonylurea or insulin. 
  • FPG is reduced about 5-10mg/dL.
  • LDL cholesterol is reduced 12-16%

Dose:

  •   Dosing for T2DM is 6*625mg tablets daily which may be split into 3 tablets twice daily.

Adverse Effects:

  • Constipation
  • Dyspepsia
  • Drug-drug interactions with Levothyroxine, Glyburide, Oral contraceptives, Phenytoin, Warfarin, Digoxin
  • Malabsorption of fat-soluble vitamins A, D, E and K 

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