I. Preparations

  1. General
    1. Lifestyle changes can lower A1C by 1-2%
    2. Efficacy Example: Weight loss, diet and Exercise
      1. Pre-intervention: HBA1C is 10%
      2. Post-intervention: HBA1C might drop to 8-9%
    3. Insulin is very cost effective (consider early especially if Hemoglobin A1C>9%)
      1. Lowers HBA1C an unlimited amount
      2. Can be used with Insulin Resistance agents
        1. Thiazolidinediones (e.g. Rosiglitazone)
        2. Metformin (Glucophage)
      3. Start with basal Insulin (e.g. Insulin Glargine or Lantus)
        1. Basal Insulin can be used with Oral Hypoglycemics
          1. Includes Sulfonylureas (cautiously)
        2. Add bolus Insulin (e.g. InsulinLispro) if Hyperglycemia persists (especially if post-prandial)
  2. Insulin Secretagogues (early Type II Diabetes)
    1. Second Generation Sulfonylurea (e.g. Glipizide, Glimepiride)
      1. Avoid Glyburide due to Hypoglycemia
      2. Lowers HBA1C by 1.5%
    2. Meglitinides (e.g. Nateglinide, Repaglinide)
      1. More expensive alternative to Sulfonylureas
      2. Lowers HBA1C by 0.5 to 1%
  3. Incretin Agents
    1. DPP-4 Inhibitors (e.g. Sitagliptin, Saxagliptin, Linagliptin)
      1. Inhibits incretin degradation resulting in Insulin secretion
      2. Lowers HBA1C by 0.5 to 1%
    2. GLP-1 Agonists (e.g. Exenatide)
      1. Incretin Mimetic that binds GLP-1 receptors and stimulates Insulin release
      2. Facilitates weight loss
      3. Lowers HBA1C by 1 to 1.5%
  4. Insulin Resistance Agents
    1. Biguanides (e.g. Metformin or Glucophage)
      1. Decreases hepatic Glucose release
      2. Lowers HBA1C by 1.5%
    2. Thiazolidinediones (e.g. Pioglitazone)
      1. Increases muscle and fat Insulin sensitivity
      2. May also independently increase cardiovascular risk (especially Rosiglitazone)
      3. Lowers HBA1C by up to 1 to 1.5%
  5. Glucose Absorption Agents
    1. Alpha-glucosidase Inhibitors (e.g. Acarbose)
      1. Decreases gastrointestinal carbohydrate absorption
      2. Lowers HBA1C by 0.5 to 1%
    2. SGLT2 Inhibitors (e.g. Invokana)
      1. Decreases renal Glucose reabsorption (allows for greater urinary excretion of Glucose)
      2. Lowers HBA1C by 1%
  6. Combination agents
    1. Actoplus Met: Pioglitazone and Metformin
    2. Duetact: Pioglitazone and Glimepiride
    3. Janumet: Sitagliptin and Metformin
    4. Metaglip: Glipizide and Metformin
    5. Avoid agents with increased risk
      1. Glucovance contains Glyburide
      2. Avandamet and Avandaryl contain Rosiglitazone

II. Protocol: Sample Template for Prescribing Combination Oral Agents

  1. General
    1. Use a combination of agents (consider from onset)
    2. Treat Insulin Resistance and Insulin shortage
    3. Lifestyle changes form the base of treatment
      1. Weight loss with calorie restriction and daily activity
      2. Carbohydrate Counting and awareness of its impact on Glucose control
  2. Step 1: Metformin (Glucophage)
    1. Most effective single agent in all patients
    2. Previously a Sulfonylurea was considered first-line in lean patients (no longer the case)
    3. Contraindicated in GFR <60 due to Lactic Acidosis risk
      1. However, there is some controversy as to what GFR level should contraindicate Metformin
    4. Consider starting with a combination agent that includes Metformin (e.g. Metaglip - Metformin with Glipizide)
  3. Step 2: Add second agent to Metformin
    1. See Step 3 for other agents to consider instead of Sulfonylureas
    2. Sulfonylurea (e.g. Glipizide, Glimepiride)
      1. Most cost effective second agent
      2. Meglitinides (e.g. Repaglinide) may be used as alternative (but more expensive)
        1. Consider for as needed pre-meal dosing in post-prandial Hyperglycemia
  4. Step 3: Add third agent
    1. Thiazolidinediones (e.g. Pioglitazone)
    2. Incretin agent (choose one)
      1. Sitagliptin (Januvia): Oral
      2. Exenatide (Byetta): Twice daily injection, but more effective and facilitates weight loss
    3. Basal Insulin (e.g. Insulin Glargine or Lantus)
      1. Consider for longer history of Type II Diabetes or if persistent HBA1C >9%
  5. Step 4: Insulin for refractory Hyperglycemia
    1. Basal Insulin (e.g. Insulin Glargine or Lantus)
    2. Bolus Insulin or pre-meal Insulin (e.g. Lispro)
      1. Stop Sulfonylurea or Meglitinide
  6. Agents with greatest effect based on timing of Hyperglycemia
    1. Pre-meal Fasting Hyperglycemia
      1. Sulfonylurea (most of effect is on pre-meal Glucose)
      2. Insulin Resistance agents
        1. Glucophage (Metformin)
        2. Thiazolidinediones (e.g. Rosiglitazone)
    2. Postprandial Hyperglycemia (Insulin deficiency)
      1. Meglitinides (e.g. Repaglinide)
      2. Alpha-glucosidase Inhibitors
  7. Agents with greatest effect based on body habitus
    1. Obese patients
      1. Metformin (Glucophage)
      2. Thiazolidinediones (e.g. Rosiglitazone)
      3. Exenatide (Byetta)
    2. Lean patients
      1. Sulfonylurea (e.g. Glipizide) or Meglitinide (e.g. Repaglinide)
      2. Sitagliptin (Januvia)
      3. Insulin

III. Adverse Effects: Oral Agents (injectables included for comparison)

  1. Hypoglycemia
    1. May account for 14% DM admissions for Hypoglycemia
    2. Highest risk with Bolus Insulin (e.g. Lispro) and should not be combined with Sulfonylureas
    3. Higher risk with Sulfonylureas (especially Glyburide) and to a lesser extent Meglitinides (e.g. Prandin)
    4. Increased risk when combined with ACE Inhibitors (especially Captopril)
  2. Weight gain
    1. Sulfonylureas
    2. Insulin
    3. Thiazolidinediones (e.g. Actos)
  3. Gastrointestinal side effects (e.g. Nausea, gas, bloating, Diarrhea)
    1. Metfiormin (Glucophage)
    2. Alpha-glucosidase Inhibitors (Acarbose, Miglitol)
    3. GLP-1 Agonist (Byetta)
  4. Pancreatitis
    1. GLP-1 Agonist (Byetta)
    2. DPP-4 Inhibitors (e.g. Januvia)
  5. Liver toxicity
    1. Thiazolidinediones (e.g. Actos)
  6. Lactic Acidosis
    1. Metformin (Glucophage)
      1. Use with caution in reduced GFR (and avoid following IV contrast)
  7. Edema (avoid in Congestive Heart Failure)
    1. Thiazolidinediones (e.g. Actos)
    2. DPP-4 Inhibitors (e.g. Januvia)
  8. Fracture risk
    1. Thiazolidinediones (e.g. Actos)
  9. Infection risk
    1. SGLT2 Inhibitors (e.g. Invokana)
      1. Adverse effects include Vaginitis and Urinary Tract Infection

IV. References

  1. (2014) Presc Lett 21(4): 19
  2. (2012) Diabetes Care 35(suppl 1): s11-63
  3. Luna (2001) Am Fam Physician 63(9):1747-56ces [PubMed] (or open in [QxMD Read])
  4. Yki-Jarvinen (2001) 24:758-67 [PubMed] (or open in [QxMD Read])

Images: Related links to external sites (from Google)

Ontology: Hypoglycemic Agents (C0020616)

Definition (MEDLINEPLUS)

Diabetes means your blood glucose, or blood sugar, is too high. If you can't control your diabetes with wise food choices and physical activity, you may need diabetes medicines. The kind of medicine you take depends on your type of diabetes, your schedule, and your other health conditions.

With Type 1 diabetes, your pancreas does not make insulin. Insulin is a hormone that helps glucose get into your cells to give them energy. Without insulin, too much glucose stays in your blood. If you have type 1 diabetes, you will need to take insulin.

Type 2 diabetes, the most common type, can start when the body doesn't use insulin as it should. If your body can't keep up with the need for insulin, you may need to take pills. Some people need both insulin and pills. Along with meal planning and physical activity, diabetes pills help people with type 2 diabetes or gestational diabetes keep their blood glucose levels on target. Several kinds of pills are available. Each works in a different way. Many people take two or three kinds of pills. Some people take combination pills. Combination pills contain two kinds of diabetes medicine in one tablet. Some people take pills and insulin.

NIH: National Institute of Diabetes and Digestive and Kidney Diseases

Definition (MSH) Substances which lower blood glucose levels.
Definition (CSP) class of agents which lower blood glucose levels.
Concepts Pharmacologic Substance (T121)
MSH D007004
SnomedCT 325290009, 373299009, 9356005, 312064005
English Agents, Hypoglycemic, Hypoglycemic Agents, hypoglycemic agent, Hypoglycemic agents, Drugs, Hypoglycemic, Hypoglycemic Drugs, Hypoglycemic drug, Hypoglycemics, Drugs for hypoglycaemia, Drugs for hypoglycemia, Hypoglycemic drug, NOS, Hypoglycaemic drug, NOS, Drugs for hypoglycemia (product), antihyperglycemic, Hypoglycaemic drug, Anti-hyperglycemics, hypoglycemic drugs, hypoglycemic agents, hypoglycaemic, hypoglycemic, hypoglycemic drug, Diabetes Medicines, Hypoglycemic Medicines, Agents, Antihyperglycemic, Antihyperglycemic Agents, Antihyperglycemics, Hypoglycaemic, Hypoglycemic agent (substance), Hypoglycemic, Hypoglycaemic agent, Hypoglycemic agent, Hypoglycaemic product, Hypoglycemic agent (product), Hypoglycemic product, Drugs for hypoglycemia (substance), Hypoglycemic drug (substance), Hypoglycemic product (product)
French Agents hypoglycémiques, Agents hypoglycémiants, Médicaments hypoglycémiants, Médicaments hypoglycémiques, Hypoglycémiants
Swedish Hypoglykemiska medel
Spanish fármacos para el tratamiento de la hipoglucemia, fármacos para el tratamiento de la hipoglucemia (producto), agente hipoglucemiante (sustancia), agente hipoglucemiante, droga hipoglucemiante (producto), droga hipoglucemiante (sustancia), droga hipoglucemiante, fármaco hipoglucemiante (producto), fármaco hipoglucemiante, hipoglucemiante (producto), hipoglucemiante, Agentes Hipoglucemicos, Agentes Hipoglucémicos
Czech hypoglykemika
Finnish Verensokeria alentavat aineet
Italian Ipoglicemici, Farmaci ipoglicemici, Sostanze ipoglicemiche
Japanese 血糖降下薬, 経口抗糖尿病薬, 抗糖尿病薬, 糖尿病薬, 糖尿病治療剤, 抗糖尿病剤, 血糖降下剤, 経口血糖降下薬
Polish Leki hipoglikemizujące, Czynniki hipoglikemizujące, Środki przeciwcukrzycowe, Środki hipoglikemiczne
German Blutzuckersenkende Mittel
Portuguese Hipoglicêmicos