Pharmacological Treatment Options in the Setting of Severe Insulin Resistance

Medication ClassA1C Lowering*Hypoglycemia RiskWeight EffectEase of UseTolerability IssuesRelative Cost
Treatment options that have been evaluated in patients with severe insulin resistance
U-500 regular insulin↓↓↓↑↑Subcutaneous; two to four times daily$$$$
GLP-1 receptor agonists↓↓←→↓↓Subcutaneous; once daily or once weeklyNausea, vomiting$$$
Metformin←→←→,↓One to four tablets once or twice dailyDiarrhea, loose stools$
Treatment options that have not been evaluated in patients with severe insulin resistance
SGLT-2 inhibitors←→Oral; once dailyUrogenital infections$$$
DPP-4 inhibitors←→←→Oral; once dailyWell tolerated$$$
TZDs←→↑↑Oral; once dailyLower extremity edema, new-onset heart failure$$$
Pramlintide↑, ←→Subcutaneous; two to three times dailyNausea, vomiting$$$$
SulfonylureasOral; once or twice daily$
Meglitinides↑, ←→Oral; two or three times daily$$
α-Glucosidase inhibitors←→←→Oral; three times dailyFlatulence, GI distress$
Colesevelam←→←→Oral; one packet or six tablets once dailyConstipation$$$
Bromocriptine←→←→Oral; four to six tablets once dailyNausea, vomiting, somnolence, rhinitis, dizziness$$$
  • * Additional A1C lowering in previously treated patients; ↓ = 0.5–1%, ↓↓ = 1–1.5%, ↓↓↓ =1.5–2%.

  • Relative cost per 30-day supply; $ = <$100, $$ = $100–299, $$$ = $300–750, $$$$ = >$750 based on average wholesale price (54).