diabetes medications

what is the epidomology of diabetes mellitus?

• ~34 million (10.5%) of the US population has DM

• 26.9 million of them were diagnosed

• 7.3 million (21.4%) were undiagnosed

what is type 1 diabetes mellitus (T1DM)?

• "insulin dependent diabetes"

• autoimmune disease in which body does not produce insulin from beta cells in pancrease

• more common in children/adolescents but can develop at any age

what is type 2 diabetes mellitus (T2DM)?

• "adult-onset diabetes"
• metabolic disorder characterized by decrease in insulin production and resistance
• most common type (~90-95% of DM in the US)

what are the types of DM?

type 1, type 2, gestational (pregnancy)

what are the risk factors of DM?

• family history (first-degree relative)
• ≧45 y/o
• obesity
• hypertension/hyperlipidemia/CVD
• history of gestational diabetes
• sedentary lifestyle

what are the hyperglycemia symptoms of DM?

• polyuria: increased urination
• polydipsia: increased thirst
• unexplained weight loss
• fatigue
• blurry vision

what are the hypoglycemia symptoms of DM?

• shakiness
• sweatiness
• hunger
• confusion
• irritability

what are the causes of hypoglycemia?

• some antidiabetic agents
• intense physical activity
• skipping meals

what is the clinical criteria of hypoglycemia?

• blood glucose (BG) less than 70 mg/dL (usual symptoms)
• if BG continues to drop and is not treat, can lead to a coma and death

how is hypoglycemia treated?

rule of 15: 15 g of sugar and re-test BG 15 min later

what is the diagnostic criteria of DM?

need 2 of the following:

• fasting blood glucose (FBG): ≧126 mg/dL
• A1C ≧ 6.5%
• OGTT ≧ 200 mg/dL
  OR
• 1 random BG ≧ 200 mg/dL with hyperglycemic symptoms

what are the microvascular complications of DM?

• retinopathy: eye damage
• nephropathy: kidney disease
• neuropathy: nerve damage

what are the macrovascular complications of DM?

• atherosclerotic cardiovascular disease (ASCVD): heart attack, stroke, coronary artery disease
• lower limb amputations

what are the general goals of treatment of DM?

• A1C < 7%
• prevent complications

what are the goals of treatment of T1DM?

• diet and exercise
• basal (long-acting) insulin
• bolus (meal-time) insulin

what are the goals of treatment of T2DM?

• diet and exercise
• antidiabetic medications
• insulin: A1C above 10% OR not controlled on multiple oral agents

what is the pharmacologic classification of -formin (biguanides)?

• decreases hepatic glucose production
• increases insulin sensitivity in peripheral muscles
• decreases absorption of glucose

what are the diabetic indications of -formin (biguanides)?

type 2 DM

what are the off-label indications of -formin (biguanides)?

gestational diabetes, prediabetes, polycystic ovary syndrome (PCOS)

what are the contraindications of -formin (biguanides)?

• eGFR < 30 mL/min
• acute/chronic metabolic acidosis

what are the adverse effects of -formin (biguanides)?

• GI: upset stomach, N/V/D
• vitamin B12 deficiency: long-term use
• lactic acidosis: rare, but serious

what are the BBWs of -formin (biguanides)?

• lactic acidosis
• bradycardia
• arrhythmias
• malaise
• somnolence
• myalgias
• respiratory dysfunction
• abdominal pain

what is the administration guidance for -formin (biguanides)?

• start low, titrate slow, and take with food to prevent GI side effects
• IR is usually administered 2-3 times/day; ER can be administered 1-2 times/day
• ER formulation has fewer side effects than IR
• must be renally dosed (look for eGFR)

what are the advantages of -formin (biguanides)?

• effective: 1-2% A1C reduction
• weight loss/neutral
• minimal to no hypoglycemia
• potential cardiovascular benefits
• cheap

what are the disadvantages of -formin (biguanides)?

• GI side effects
• renal dose adjustments

what is the pharmacologic classification of -gliflozins?

• increases glucose excretion in the urine
• decreases reabsorption of glucose

what are -gliflozins?

• sodium-glucose co-transporter 2 inhibitors (SGLT2i's)
• jardiance (empagliflozin), invokana (canagliflozin), dapagliflozin (farxiga), steglatro (ertugliflozin)

what are the diabetic indications of -gliflozins?

• T2DM: all
• ASCVD reduction: empagliflozin and canagliflozin only
• diabetic kidney disease: empagliflozin, canagliflozin, and dapagliflozin
• heart failure: all

what are the contraindications of -gliflozins?

end-stage renal disease (dialysis)

what are the adverse effects of -gliflozins?

• common: genitourinary infections and hypotension/volume depletion
• necrotizing fasciitis and ketoacidosis (rare)
• lower limb amputation and bone fractures: rare; canaglifozin only

what is the administration guidance of -gliflozins?

• administer once daily in the morning (increases urination)
• caution in renal impairment: cannot initiate canagliflozin if eGFR <30 mL/min; dapagliflozin if eGFR <25 mL/min; empagliflozin if <20 mL/min

what are the advantages of -gliflozins?

• use for T2DM and other comorbidities
• minimal hypoglycemia
• weight loss
• lowers BP

what are the disadvantages of -gliflozins?

• low efficacy: 0.5-0.9% A1C reduction
• many rare but serious side effects
• UTI's are common in women and in those with higher A1Cs

what are -gliptins?

• dipeptidyl peptidase 4 (DPP-4) inhibitor
• januvia (sitaglitpin), alogliptin (nesina), onglyza (saxagliptin), tradjenta (linagliptin)

what is the pharmacologic classifcation of -gliptins?

• food intake + incretins = increased insulin and decreased glucagon
• DPP-IV enzyme inhibits process: drugs prevent inhibition

what are the indications of -gliptins?

type 2 DM only

what are the contraindications of -gliptins?

• history of pancreatitis
• HF caution (saxagliptin and alogliptin only)

what are the adverse effects of -gliptins?

• common: upper respiratory tract infections and nasopharyngitis
• joint pain (rare)

what is the administration guidance for -gliptins?

• administer once daily without regards to meals
• no dose titration: dose is based on renal function (eGFR)

what are the advantages of -gliptins?

• well-tolerated
• minimal hypoglycemia
• weight neutral

what are the disadvantages of -gliptins?

low efficacy: 0.5-1% A1C reduction

what are -tides?

• glucagon-like peptide-1 (GLP-1) receptor agonists
• byetta/bydureon bcise (exenatide), liraglutide (victoza), trulicity (dulaglutide), ozempic/rybelsus (semaglutide)

what is the pharmacologic classification of -tides?

• increases insulin, weight loss, and beta cells
• decreases glucagon and gastric emptying

what are the indications of -tides?

• type 2 DM only
• ASCVD prevention: liraglutide, semaglutide subcutaneous only, dulaglutide
• weight management: liraglutide (saxenda), semaglutide (wegovy)

what are the contraindications of -tides?

• medullary thyroid cancer
• multiple endocrine neoplasia syndroms type 2
• history of pancreatitis

what are the adverse effects of -tides?

• GI side effects: upset stomach, N/V/D, GERD
• injection site reactions

what is the administration guidance of -tides?

• start low and go slow to minimize GI side effects
• dulaglutide, exanitide ER, and ozempic dosed once weekly
• rybelsus must be adminstered with 4 oz of water without other medications or food for at least 30 minutes

what are the advantages of -tides?

• effective 1-2% A1C reduction
• weight loss
• minimal hypoglycemia
• some have ASCVD protection

what are the disadvantages of -tides?

• expensive
• GI side effects common but subside with time

what is tirzepatide (mounjaro)?

• dual GLP/GIP: works like GLP, but also mimics GIP, which increases insulin secretion
• most weight loss and A1C lowering of any non-insulin medication
• dose is 2.5-15mcg SC once weekly
• similar administration as dulaglutide

what are -rides, -zides, -glus, and -glis?

• sulfonylureas
• glipizide (glucotrol), glimepiride (amaryl), glyburide (diabeta, micronase)

what is the pharmacologic classification of -rides, -zides, -glus, and -glis?

increases secretion of insulin in pancreatic beta cells

what are the indications of -rides, -zides, -glus, and -glis?

type 2 DM only

what are the contraindications of -rides, -zides, -glus, and -glis?

• hypersensitivity to other sulfonylureas
• sulfonamide reaction (caution)

what are the adverse effects of -rides, -zides, -glus, and -glis?

• hypoglycemia (glyburide has highest risk)
• weight gain

what is the administration guidance of -rides, -zides, -glus, and -glis?

• administered once or twice daily with food to avoid hypoglycemia
• caution in kidney disease: glyburide NOT recommended in chronic kidney disease
• use lower doses in patients at high risk of hypoglycemia (elderly, skip meals, exercise, vigorously)

what are the advantages of -rides, -zides, -glus, and -glis?

• effective: 1-1.5% A1C reducion
• cheap

what are the disadvantages of -rides, -zides, -glus, and -glis?

• hypoglycemia risk
• weight gain
• beta cell burnout: lose efficacy with time

what is -glitazone?

• thiazolidinediones (TZDs)
• rosiglitazone, pioglitazone (actos)

what is the pharmacologic classification of -glitazone?

• PPAR activation
• increases cell response to insulin
• decreases insulin resistance

what are the indications of -glitazone?

type 2 DM only

what are the contraindications of -glitazone?

NYHA class III/IV heart failure

what are the adverse effects of -glitazone?

• common: edema and weight gain
• increased risk of bladder cancer (rare)
• increased risk of fractures (rare)

what is the administration guidance of -glitazone?

• may be administered once daily without regards to meal
• caution in hepatic impairment (increased LTFs, jaundice, dark urine)

what is the formulation of pioglitazone?

tablets: 15mg, 20mg, 45mg

what are the advantages of -glitazone?

• effective: 1-1.5% A1C reduction
• cheap
• minimal hypoglycemia
• increases insulin sensitivity (alternative to metformin)

what are the disadvantages of -glitazone?

• edema
• weight gain
• HF, fracture and bladder cancer risk

what are -glinides (meglitinides)?

• second-line agents for T2DM
• repaglinide (prandin), nateglinide (starlix)

what is the pharmacologic classification of -glinides (meglitinides)?

increased secretion of insulin in pancreatic beta cells that is glucose-dependent

what are the indications of -glinides (meglitinides)?

• type 2 DM only
• not recommended in pregnancy

what are the contraindications of -glinides (meglitinides)?

hypersensitivity to other agents

what are the adverse effects of -glinides (meglitinides)?

• hypoglycemia
• weight gain
• upper respiratory infection

what is the adminstration guidance of -glinides (meglitinides)?

• administer 15-30 min before each meal up to 3 times a day
• skip dose if skips a meal

what are the advantages of -glinides (meglitinides)?

• rapid onset and shorter duration
• flexible dosing compared to sulfonylureas

what are the disadvantages of -glinides (meglitinides)?

• low efficacy: 0.5-1% A1C reduction
• hypoglycemia risk
• generic but "expensive"

what are alpha-glucosidase inhibitors?

• second-line agents for T2DM
• acarbose (precose), miglitol (glyset)

what is the pharmacologic classification of alpha-glucosidase inhibitors?

• inhibits alpha-glucosidase in intestinal brush border
• stops hydrolysis of carbs to monosaccharides
• delays absorption of glucose
• reduces postprandial glucose

what are the indications of alpha-glucosidase inhibitors?

type 2 DM only

what are the contraindications of alpha-glucosidase inhibitors?

• inflammatory bowel disease, digestive disorders, disorders prone to bowel obstruction
• diabetic ketoacidosis
• cirrhosis

what are the adverse effects of alpha-glucosidase inhibitors?

flatulence, abdominal pain, diarrhea

what is the administration guidance of alpha-glucosidase inhibitors?

• administer with first bite of each meal up to 3 times a day
• skip dose if skip a meal
• caution in renal impairment; contraindicated in patients with cirrhosis

what is the formulation of acarbose and miglitol?

tablets: 25mg, 50mg, 100mg

what are the advantages of alpha-glucosidase inhibitors?

• rapid onset and shorter duration
• flexible dosing compared to sulfonylureas
• targets PPG readings

what are the disadvantages of alpha-glucosidase inhibitors?

• low efficacy: 0.5-1% A1C reduction
• GI side effects
• generic yet "expensive"

what is the formulation of metformin?

• immediate release (IR): 500mg, 850mg, 1000mg
• extended release (ER): 500mg, 750mg, 1000mg
• tablets, liquid

what is the formulation of -gliflozin?

tablets

what is the formulation of -liptins?

tablets

what is the formulation of dulaglitide and liraglutide?

injection pen

what is the formulation of exanitide?

injection pen and ER autoinjector

what is the formulation of semaglutide?

• rybelsus: tablets
• ozempic: injection pen

what is the formulation of glipizide?

IR andXL tablets

what is the formulation of glimeizide?

IR tablets

what is the formulation of glyburide?

IR and micronized

what is the formulation of nateglinide and repaglinide?

tablets