TABLE 2.

Pharmacological Treatment Options in the Setting of Severe Insulin Resistance

Medication Class	A1C Lowering*	Hypoglycemia Risk	Weight Effect	Ease of Use	Tolerability Issues	Relative Cost†
Treatment options that have been evaluated in patients with severe insulin resistance
U-500 regular insulin	↓↓↓	↑	↑↑	Subcutaneous; two to four times daily		$$$$
GLP-1 receptor agonists	↓↓	←→	↓↓	Subcutaneous; once daily or once weekly	Nausea, vomiting	$$$
Metformin	↓	←→	←→,↓	One to four tablets once or twice daily	Diarrhea, loose stools	$
Treatment options that have not been evaluated in patients with severe insulin resistance
SGLT-2 inhibitors	↓	←→	↓	Oral; once daily	Urogenital infections	$$$
DPP-4 inhibitors	↓	←→	←→	Oral; once daily	Well tolerated	$$$
TZDs	↓	←→	↑↑	Oral; once daily	Lower extremity edema, new-onset heart failure	$$$
Pramlintide	↓	↑, ←→	↓	Subcutaneous; two to three times daily	Nausea, vomiting	$$$$
Sulfonylureas	↓	↑	↑	Oral; once or twice daily		$
Meglitinides	↓	↑	↑, ←→	Oral; two or three times daily		$$
α-Glucosidase inhibitors	↓	←→	←→	Oral; three times daily	Flatulence, GI distress	$
Colesevelam	↓	←→	←→	Oral; one packet or six tablets once daily	Constipation	$$$
Bromocriptine	↓	←→	←→	Oral; four to six tablets once daily	Nausea, vomiting, somnolence, rhinitis, dizziness	$$$

^*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).