Download Type 2 Diabetes - Andrew N. Schmelz, PharmD

Diabetes Crash Course:
The Outpatient Setting
Dr. Andrew Schmelz, PharmD
Post-Doctoral Teaching Fellow
Purdue University
October 7, 2008
[email protected]
Objectives
Upon completion of this crash course,
clerkship students will be able to:
 Differentiate characteristics of Type 1 and Type 2
diabetes mellitus
 Describe the literature supporting intensive
therapy for treating hyperglycemia
 State goals of therapy for patients with DM
 Organize antidiabetic agents into groups based
on place in DM pharmacotherapy
 Recommend an appropriate medication regimen
for DM based on patient-specific parameters
Major Classifications
Type 1 Diabetes – results from β-cell
destruction, usually leading to absolute
insulin deficiency
 Type 2 Diabetes – results from a
progressive insulin secretory defect on the
background of insulin resistance
 Gestational Diabetes – diagnosed during
pregnancy

Clinical Trials
DCCT: Type 1 patients
– Improved glycemic control reduces the risk
and slow the progression of microvascular
disease
 EDIC: Type 1 patients
– Improved glycemic control protects against
the occurrence of macrovascular disease
 UKPDS: Type 2 patients
– Strict glycemic control results in a reduction in
risk of microvascular disease

Decrease in A1C
 Secondary
analysis revealed that a
1% decrease in A1C was associated
with:
–35% reduction in microvascular
endpoints
–18% reduction in MI
–17% reduction in all-cause
mortality
Glycemic Goals
A1C is primary target for glycemic control
 A1C goal for patients in general is 7%
 A1C goal for the individual patient is as close to
< 6% as possible without significant
hypoglycemia

Antidiabetic
Medications
Patient Case
Biguanides

Example: Metformin (Glucophage)
– 500 mg daily or BID, Max: 2550 mg/day
Lowers A1c 1.5-2%  FIRST LINE AGENT
 MOA: Decreases hepatic glucose
production, increase response to insulin
 Contraindications
– SCr > 1.5 (males) or 1.4 (females)
– Acute/chronic metabolic acidosis
– HF requiring treatment

Biguanides (cont)

Adverse Effects
– GI: Diarrhea, flatulence, nausea
– Metallic taste
– Lactic acidosis

Monitoring
– Therapeutic: A1c, FPG
– AE: SCr (therapy initiation and annually), BMP,
intolerance

Bottom Line: Usually first choice for
Type II patients unless contraindicated
Sulfonylureas

Examples:
– Glipizide (Glucotrol) 5 mg daily before
breakfast, Clinical max: 20 mg daily
– Glyburide (DiaBeta, Micronase)
– Glimepiride (Amaryl)
Lower A1c 1.5-2%  FIRST LINE AGENT
 MOA: Increase insulin secretion
 Contraindications: Hypersensitivity (sulfa)

Sulfonylureas (cont)

Adverse Effects
– Hypoglycemia
– Some weight gain
– Allergic skin reactions / photosensitivity

Monitoring
– Therapeutic: A1c, FBG
– AE: FBG

Bottom Line: Also used near initiation of
therapy
Thiazolidinediones

Examples:
– Pioglitazone (Actos) 15 mg daily, Max 45 mg
daily
– Rosiglitazone (Avandia)
Lower A1c 1.0%  Alternative agent
 MOA: inhibit PPAR-gamma (improves
cellular response to insulin)
 Contraindications: CHF (also macular
edema, risk for MI)

TZDs (cont)

Adverse Effects
– Hepatotoxicity (troglitazone pulled from
market)
– Exacerbation of CHF
– Macular edema

Monitoring
– Therapeutic: A1c, FBG
– AEs: LFTs (baseline, periodically, d/c if >3 X
ULN), CHF sxs, visual disturbances

Bottom Line: Use only if near A1c goal
Alpha-Glucosidase Inhibitors

Examples:
– Acarbose (Precose) 25 mg 15-30 mins AC,
Max 300 mg daily
– Miglitol (Glyset)
Lower A1c < 1.0%  Special niche only
 MOA: inhibit intestinal alpha-glucosidase
 Contraindications: DKA, IBD, colonic
ulceration, intestinal obstruction

AGIs (cont)

Adverse effects
– GI: flatulence, diarrhea, abdominal
pain/cramps
– Rash
– Increased LFTs

Monitoring
– Therapeutic: A1c, FBGs, post-prandial glucose
– AE: LFTs, s/sxs rash, intolerance

Bottom Line: Only for lowering PPG
Meglitinides

Examples:
– Repaglinide (Prandin) 4 mg TID with meals,
Max 12 mg TID
– Nateglinide (Starlix)
Lower A1c 0.8-1%  Special niche only
 MOA: Stimulate insulin secretion
 Contraindications: Really, none

Meglitinides (cont)

Adverse Effects
– Hypoglycemia (less than SUs)
– Weight gain

Monitoring
– Therapeutic: A1c, FBGs
– AE: FBG

Bottom Line: Alternative for pts unable
to take sulfonylurea
GLP-1 System Drugs

First example:
– Exenatide (Byetta) 5 mcg SQ BID, Max 10
mcg BID
Lowers A1c 0.8-1%  Alternative agent
 MOA: Synthetic GLP-1
 Contraindications: Really, none

GLP-1 System Drugs (cont)

Adverse Effects
– Nausea (dose-dependant)
– Hypoglycemia
– Pancreatitis

Monitoring
– Therapeutic: A1c, FBGs
– AEs: FBGs

Bottom Line: New drug, place in therapy
TBD
GLP-1 System Drugs (cont)

Second example:
– Sitagliptin (Januvia) 100 mg daily (lower
doses per renal function)
Lowers A1c 0.7-0.8  Alternative agent
 MOA: inhibits DDP-IV
 Contraindications: Really, none

GLP-1 System Drugs (cont)

Adverse Effects
– Very little HA

Monitoring
– Therapeutic: A1c, FBGs

Bottom Line: New drug, place in therapy
TBD
Amylin Analogs

Example:
– Pramlintide (Symlin) 60 mcg before meals,
Max 120 mcg
Lowers A1c 0.5-0.6  Not very good,
used in combination with insulin
 MOA: Synthetic analog of amylin
 Contraindications: Really, none

Amylin Analogs (cont)

Adverse effects
– NV, anorexia (decrease over time, delay dose
increase until nausea resolves)
– Hypoglycemia

Monitoring
– Therapeutic: A1c, FBGs
– AEs: FBGs, sxs NV

Bottom Line: Utility? Only agent besides
insulin for Type 1 patients
Comparison
FBG ↓
(mg/dL)
Agent
A1C ↓
Hypoglycemia
Weight
Effects
Sulfonylureas
50-60
1.5-2
Yes
Gain
Metformin
50-78
1.5-2
No
-
α-glucosidase
inhibitors
10-25
<1.0
No
-
Thiazolidinediones
45-65
1.0
No
Gain
Meglitinides
30-50
0.8-1
Yes
Gain
Exenatide
10-25
0.8-1
No
Loss
Sitagliptin
15-20
0.7-0.8 No
-
Pramlintide
10-20
0.5-0.6 Yes
Loss
Insulin
↓↓
>2.0
Gain
Yes
Insulins

Rapid-acting
Peak ~ 1 hour
– Lispro (Humalog), Aspart (Novolog), Apidra
(Glulysine)

Fast-acting
Peak ~ 3 hours
– Regular (Humulin R, Novolin R)

Intermediate-acting
Peak ~ 8 hours
– NPH (Humulin N, Novolin N)

Long-acting
– Glargine (Lantus), Detemir (Levimir)
AS Case (cont)
Lantus 34 units QHS and Humalog 6 units before meals
Date
2/03
2/04
2/05
2/06
2/07
2/08
2/09
2/10
Breakfast
197
Lunch
Dinner
298
70
220
Bedtime
178
276
67
260
145
259
58
234
121
267
72
132