Medications For Diabetes Mellitus

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Goals of treatment for Diabetes Mellitus

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Improve symptoms of diabetes
Prevent metabolic complications (ketoacidosis)
Prevent long term complications
Reduce glucose and A1C to acceptable levels

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Average prprandial blood glucose

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ADA: 80-120 AACE: 110

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Average 2hr postprandal glucose

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ADA < 180 AACE <140

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Average bedtime glucose

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ADA 110-140

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A1C Goal

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ADA < 7.0% AACE <6.5%

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Mechanism of action for Insulin

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replaces insulin

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Side effects of Insulin

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hypoglycemia
Allergic reactions at the site of injection
Lipodystrophy

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Special considerations for Insulin

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Rotate sites
If refrigerated, unopened bottles are good through the expiration date
Once opened, usually good for 1 month
Store away from light
Roll bottle between palms to re-suspend suspensions
Always draw up reg first
Reg insulin is the only type for IV use

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Mechanism of action for sulfonylureas

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Increase release of endogenous insulin and increases insulin sensitivity at peripheral sites

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Examples of Sulfonylureas

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Glucatrol
Diabeta

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Side effects of sulfonylureas

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hypoglycemia
weight gain
disulfiram-like reaction (chlorpropamide)
Dilutional hyponatremia (Chlorpropamide)

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Special considerations for sulfonylureas

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Contraindicated in patients with sulfa allergy
Elderly more prone to hypoglycemia
Can be used as monotherapy but most patients show eventual decline in glucose control

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Mechanism of action for biguanides

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inhibits hepatic production of glucose

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Example of biguanides

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Metformin (Glucophage)

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Side effects of biguanides

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Diarrhea
Nausea, vomiting
Abdominal discomfort
Lactic acidosis (promarily in pats with renal insufficiency)

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Special considerations for biguanides

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does not cause hypoglycemia or weight gain
induces modest weight loss in most patients
Tolerance develops in most cases to GI effects
Contraindications to include:SrCr >1.5 mg/dL on men or > 1.4 mg/dL in women; radiologic studies involving IV contrast dyes; CHF and significant liver disease; dehydration

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Mechanism of action for Alpha-Glucosidase Inhibitors

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inhibits Alpha-glucosidase enzymes in the small intestine which slows digestion of ingested carbohydrates and thus delays glucose absorption

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Examples of Alpha-Glucosidase Inhibitors

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Acarbose
Miglitol

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Side Effects of Alpha-Glucosidase

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Diarrhea
Bloating
Flatulence
(GI effects are really bad and don't go away...given right before meals)

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Special considerations for Alpha-Glucosidase Inhibitors

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GI effects limit their use
Do not cause hypoglycemia when used as monotherapy
Given with each meal to prevent postprandial glucose spikes

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Mechanism of action for thiazolidinedione

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increase insulin sensitivity in muscle

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Examples of thiazolidinedones

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Rosiglitazone, Pioglitazone

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Side effects of thiazolidinedione

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weight gain
peripheral edema
idiosuncratic hepatovellular injury
Anemia

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Special considerations for thiazolidinediones

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do not cause hypoglycemia when used as monotherapy
Slow onset of action over 16 weeks
Monitor liver enzymes every 2 months for first year
Most expensive agents available
Contraindications: stage III or IV heart failure; liver abnormalities
Rosiglitazone may be associated with increased risk of heart attack

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Mechanism of action for non-sulfonylreas

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stimulate insulin secretion from the pancreas

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Side effects of non-sulfonylureas

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hypoglycemia
weight gain

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examples of non-sulfonylureas

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repaglinide, nateglinide

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special considerations for non-sulfonylureas

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only given with meals because of fast onset and short duration of action
main advantage is lowering of postprandial glucose
add or omit does if meal is added or omitted
expensive

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Example of incretin mimetic

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Byetta

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Mechanism of action for incretin mimetics

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stimulates insulin secretion by causing increased beta cell growth and replication; also slows gastric emptying and may decrease food intake

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Side effects of increin mimetic

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hypoglycemia
GI effects
dizziness, headache

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Special considerations of incretin mimetics

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administerd with sulfonylureas and/or metoformin
May cause weight loss
administer drugs which require optimal absorption one hour before byetta
administered twice daily-injections

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Mechanism of action of DPP4 Inhibitors

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Inhibit the breakdown of increin by dipptidyl peptidase IV, thus promoting insulin secretion

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Examples of DPP4 Inhibitor

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Januvia

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Side effects of DPP4-Inhibitors

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Upper respiratory tract infection
Stuffy or runny nose and sore throat
Headache

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Special considerations for DPP4 Inhibitors

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Usually used as second line agent
Lowers HbA1c 0.6-0.8
Does not appear to cause weight loss or nausea

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Mechanism of action for Amylin Agonists

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Mimics the action of naturally occuring pancreatic hormone amylin. By doing so, glcemic control s improved through the modulation of gastric emptying, prevention of postprandial rise in glgacon levels, and by increasing levels of satiety

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Side effects of Amylin Agonists

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nausea
anorexia, vomiting, and abdominal pain
weight loss

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Special considerations for Amylin Agonists

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only indicated for use with insulin
give sq before meals
preprandial rapid or short acting insulin doses must be reduced in order to reduce the risk of hypoglycemia

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IDDM
Two daily injections with starting total daily dose of 0.6 units/kg.day

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Combination of NPH and Reg before breakfast and before evening meal
Two thirds of toal dose given in morning and one-third in evening
Intermediate insulin (NPH) should compromis 2/3 of morning dose and 1/2 of evening dose

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IDDM Four daily injections with starting daily dose of 0.6 units/kg/day

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Basal insulin (Glargine) should be 45% of total daily dose
Prandial insulin (Lispro, Aspart) should be given 25% of toal before breakfast and 15% before lunch and dinner
Most patients require 0.5-1.0 units/kg/day

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IDDm

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Give enteric coated aspirin to all patients > 30 years old if no contraindications

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NIDDM
First step

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Lifestyle modifications and initiate metformin 500 mg qd-bid titratinf up to 850-1000 mg BID (unless they have renal dysfunction, increased LFTs, heart failure)

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In NIDDM, if after 3 months HbA1c is greater than 7% then

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add Sufonylurea or basal insulin or Pioglitzone or Rosiglitazone
If after 3 months, it is still high, add an additional agent or intensify insulin for those patients on insulin.