IP3 Non-Insulin Pharmacology

Sulfonylurea MOA

Bind SUR/Kir6.2 → close K⁺ channels → depolarization → Ca²⁺ influx → insulin release

Sulfonylurea Clinical Use

Requires functional β-cells → not for T1DM

Sulfonylurea ADRs

Hypoglycemia, weight gain

Sulfonylurea CI

Pregnancy, lactation, severe renal/hepatic impairment

Sulfonylurea Origin

Derived from sulfa antibacterial agents with urea moiety

Glyburide PK

Active metabolites → prolonged hypoglycemia risk

Glimepiride Brand

Amaryl

Glipizide Brand

Glucotrol

Glyburide Brand

Glynase

Sulfonylurea Mechanism Category

↑ insulin secretion

Glinide MOA

Same as SUs but faster onset/shorter duration → targets PPG

Glinide Pearls

Take before meals; safe in sulfa allergy

Glinide Metabolism

CYP2C9/3A4

Repaglinide Brand

Prandin

Nateglinide Brand

Starlix

Repaglinide Mechanism Category

↑ insulin secretion

Nateglinide Mechanism Category

↑ insulin secretion

GLP-1 RA MOA

↑ glucose-dependent insulin secretion, ↓ glucagon, ↓ gastric emptying, ↑ satiety

GLP-1 RA Structural Pearl

Modified to resist DPP-4 degradation (Ala substitution)

GLP-1 RA Albumin Binding

Enhances half-life (e.g., C16 acyl chain in liraglutide)

GLP-1 RA ADRs

GI upset, nausea, vomiting

GLP-1 RA Black Box

Risk of MTC/MEN2

Exenatide CI

Avoid if CrCl < 30 mL/min

Dulaglutide Brand

Trulicity

Liraglutide Brand

Victoza / Saxenda

Semaglutide Brand

Ozempic / Rybelsus / Wegovy

Exenatide Brand

Bydureon BCise

GLP-1 RA Mechanism Category

↑ insulin secretion

DPP-4i MOA

Inhibit DPP-4 → ↑ endogenous GLP-1/GIP → ↑ insulin, ↓ glucagon

DPP-4i PK

Sitagliptin: renal; Linagliptin: hepatobiliary; Alogliptin: renal

DPP-4i ADRs

Nasopharyngitis, headache, rare joint pain

Sitagliptin Brand

Januvia

Linagliptin Brand

Tradjenta

Alogliptin Brand

Nesina

DPP-4i Mechanism Category

↑ insulin secretion

Metformin MOA

Activates AMPK → ↓ hepatic gluconeogenesis, ↑ insulin sensitivity

Metformin Transport

Enters via OCT1; inhibits mitochondrial ATP → ↑ AMP → activates AMPK

Metformin ADRs

GI upset, lactic acidosis (rare)

Metformin CI

eGFR < 30 mL/min

Metformin PK

No metabolism; renal excretion via OCT/MATE

Metformin Brand

Glucophage

Metformin Mechanism Category

↑ insulin sensitivity

TZD MOA

Activate PPAR-γ → ↑ GLUT-4, ↑ adiponectin → ↓ insulin resistance

TZD Pearls

Weight gain, edema, fracture risk; avoid in CHF

TZD PK

Hepatic metabolism (Pioglitazone: CYP2C8/3A4; Rosiglitazone: CYP2C9/3A4)

Pioglitazone Brand

Actos

Rosiglitazone Brand

Avandia

TZD Mechanism Category

↑ insulin sensitivity

AGI MOA

Inhibit brush border enzymes → delay carb digestion → ↓ PPG

AGI ADRs

Flatulence, diarrhea

AGI CI

Acarbose: GI disease; Miglitol: renal failure

Acarbose Brand

Precose

Miglitol Brand

Glyset

Acarbose Mechanism Category

↓ glucose absorption

Miglitol Mechanism Category

↓ glucose absorption

SGLT2i MOA

Inhibit SGLT2 in proximal tubule → ↑ glucose excretion

SGLT2i Pearls

CV/renal protection; risk of euglycemic DKA, genital infections

SGLT2i PK

Hepatic glucuronidation; renal elimination

Canagliflozin Brand

Invokana

Dapagliflozin Brand

Farxiga

Empagliflozin Brand

Jardiance

Ertugliflozin Brand

Steglatro

SGLT2i Mechanism Category

↑ glucose excretion

Bromocriptine MOA

D2 agonist → ↓ sympathetic tone → ↓ hepatic glucose production

Bromocriptine ADRs

Nausea, dizziness, orthostasis

Bromocriptine Brand

Cycloset

Bromocriptine Mechanism Category

↓ glucose production

Colesevelam MOA

Binds bile acids → ↑ GLP-1, ↓ hepatic glucose production

Colesevelam ADRs

Constipation, ↑ TGs; separate meds by 4 hrs

Colesevelam Brand

Welchol

Colesevelam Mechanism Category

↓ glucose production

Pramlintide MOA

↓ glucagon, ↓ gastric emptying, ↑ satiety

Pramlintide ADRs

Nausea, hypoglycemia (with insulin)

Pramlintide Brand

Symlin

Pramlintide Mechanism Category

↓ postprandial glucose