- DM - 2:
- Pathogenesis:
- Insulin deficiency (relative
- Insulin resistance (92%)
- Excess Glucagon
- Decreased Amylin
- GLP1 effectiveness is decreased along with total amount of GLP1
- Increased renal glucose reabsorption
- CNS defects
- Rapid Gastric Emptying
- Abnormal Appetite
- Glucose Toxicity: Chronic elevation of glucose causes more Insulin release, but also increases resistance putting the body in the vicious cycle.
- Lipotoxicity: Causes insulin resistance
- Screening:
- BMI of 23 for Asian American
- Diagnosis:
- Monitoring:
- Treatment:
- Goal:
- Pre-meal goal: 80-130 mg/dL (ADA- 2015)
- UKPDS: Newly Diagnosed DM:
- UKPDS 10 yr follow up :
- ACCORD Study
- Oral Anti-hypoglycemics:
- Insulin Secretogugues
- Sulfonylureas
- Also, effects basal and post-prandile glucose level
- MOA: Binds to Sulphonylurea receptor in Beta Cells - close KATP channel - open Ca++ channel - Insulin released - this action is independent of blood glucose level
- Glyburide
- Metobolite has hypoglycemic effect
- Glimepiride (Amaryl) 1-4 mg / day once a day
- Glipizide (Glucotrol)
- Non-sulfonylurea Insulin Secretogogues
- MOA: Same as in Sulfonylurea - hence, not used in combination with SU
- Repaglinide (prandin)
- Good for patient with allergy to sulfa
- Not frequently used
- Nateglinide (not used)
- Insulin Sensitizer (Predominent site of action is different, hence, can be combined together)
- Can be combined with Insulin
- Thiozolidinediones (TZD)
- MOA: PPAR-Gamma
- Despite increased in weight (part of it due to increased adipose tissue, it decrease visceral adipose tissue, increasing the insulin sensitivity
- Seen more in patients who are also in Insulin. Of note, Insulin itself causes these changes
- Predominent effect on Muslce and Adipose Tissue
- Pioglitozone,
- Rosiglitozone (not used any more)
- Biguanides (Metformin, Metformin XR)
- Predominent effect on Liver
- MOA: Not clear
- Alpha-glucosidase inhibitors (Acarbose, Miglitol)
- DPP-IV Inhibitors
- Does not have long lasting effect
- Incretin and GLP-1 pathways
- SE: HA, URT Symptoms, N / D
- Sitaglipton (Januvia),
- Saxaglipton (Onglyza) - increased heart failure in one study,
- Linaglipton (Tradjenta) Medicaid 2017: Covered
- Aloglipton (Nesina)
- SGLT-2 Inhibitors
- 1% drop in A1C; Increased LDL, Mycotic Infection
- Possible Increase in CV events
- Canaglifozin (Invokana) Medicaid 2017: Not Covered
- Empaglifozin (Jardiance) Medicaid 2017: Not Covered
- Dapaglifozin (Farxiga) Medicaid 2017: Not Covered
- Injectable Anti-hypoglycemics:
- GLP-1 Agonists
- Binds to many cells in body including Beta cells in pancreas - GLP1 Receptor - acts as agnoists
- MOA:
- Glucose Dependent Insulin Secretion
- Delayed gastric emptying
- Suppression of glucagon
- Decreased appetite and weight loss
- Exenatide IR (byetta) twice daily / Exenatide ER (once weekly) (Bydureon) Ref_ uptodate
- Bydurean: Medicaid 2017: Covered
- Immediate release: Initial: 5 mcg twice daily within 60 minutes prior to a meal; after 1 month, may be increased to 10 mcg twice daily (based on response)
-
Extended release: 2 mg once weekly
Note: May administer a missed dose as soon as noticed if the next regularly scheduled dose is due in ≥3 days; resume normal schedule thereafter. To establish a new day of the week administration schedule, wait ≥3 days after last dose given, then administer next dose on new desired day of the week.
- Liraglutide (Victoza)
Chronic weight management: SubQ: Initial: 0.6 mg once daily for one week; increase by 0.6 mg daily at weekly intervals to a target dose of 3 mg once daily. If the patient cannot tolerate an increased dose during dose escalation, consider delaying dose escalation for one week. If the 3 mg daily dose is not tolerated, discontinue use as efficacy has not been established at lower doses.
Note: Evaluate change in body weight 16 weeks after initiation of therapy; discontinue if at least 4% of baseline body weight loss has not been achieved.
Diabetes mellitus, type 2: SubQ: Initial: 0.6 mg once daily for 1 week; then increase to 1.2 mg once daily; may increase further to 1.8 mg once daily if optimal glycemic response not achieved with 1.2 mg daily.
Note: Initial dose is intended to reduce GI symptoms; does not provide effective glycemic control.
Missed doses: In the event of a missed dose, the once daily regimen can be resumed with the next scheduled dose (an extra dose or an increase in the next dose should not be attempted); if >3 days have passed since the last liraglutide dose, reinitiate therapy at 0.6 mg/day to avoid GI symptoms and titrate according to prescriber discretion.
- Abliglutide (once weekly) (Tanzeum)
- Dulaglutide (once weekly) (Trulicity)
- More skin issues with Bydureon
- More GI side effects with Trulicity
- Tanzeum is not as potent as Bydureon or Trulicity, and does not cause weight loss.
- Amylin (Pancreatic Hormones) Agonists
- Pramlintide
- Preprandile dosing: 60 mg or 120 mg SC Inj
- Mealtime Insulin should be decreased by 50% to avoid hypoglycemic episodes
- Insulin: See type DM 1
- Additional References
Type 2 DM across generations: from pathophysiology to prevention and management Lancet 2011
Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes Lifestyle Change and Mobility in Obese Adults with Type 2 Diabetes Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabete
Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy ARB versus ACEI in Type 2 Diabetes and Nephropathy Preventing Microalbuminuria in Type 2 Diabetes
BMJ 2017;356:i6505
doi: 10.1136/bmj.i6505
Diabetes Mellitus
Pharmacology in Endocrinology DM 2

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