DM : Outpatient

  • 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

    • 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) 
              • BID 
              • Xl - Once a day 
        • 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
Statin in DM : 

Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes

Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes
Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death
Severe Hypoglycemia and Risks of Vascular Events and Death
Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance
A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease
Intensive versus Conventional Glucose Control in Critically Ill Patients

Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events ONTARGET
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes
Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus
Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events
Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults
A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease
Three-Year Efficacy of Complex Insulin Regimens in Type 2 Diabetes
Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes
Glucose Regulation in Young Adults with Very Low Birth Weight

In-patient Blood Glycemic Management
Intensive versus Conventional Glucose Control in Critically Ill Patients The NICE-SUGAR Study Investigators*
Intensive Insulin Therapy in the Medical ICU
Type 1 DMRenal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes
GAD65 Antigen Therapy in Recently Diagnosed Type 1 Diabetes Mellitus
Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes
Type 1 diabetes, hyperglycemia, and the heart Lancet 2008

Pharmacology in Endocrinology
DM 2