Medication Titration Algorithm for Type 2 Diabetes ¹ V2.1 updated 6/1/2017
Hemoglobin A1c AM SMBG³ Goals²: < 65 yrs <7% 70-130 ≥ 65 yrs <8% 100-160 Metformin + Lifestyle Modifications Basal Long Acting < 2% > 2% Insulin ⁴ Above Above Goal Goal 10 units SQ at hs ↑ 2 units q. 2 days until at target
Educate about Start Metformin Use optimal hypoglycemia Contraindications: 500 mg: titration intervals - eGFR <30 to help patient - HF class 3-4 ½ tablet bid → 1 tablet bid → - LFTs>3xULN 2 tablets bid reach goal ASAP CAUTION: eGFR < 45 Titrate q. 1-2 weeks aiming →Use Alternate Agent for AM SMBG target³ Insulin therapy should not be Thiazoladinedione delayed (Pioglitazone) $
Not At At Goal After 3 Goal months Meglitinides $$
Maintain Dual Therapy A-glucosidase Risk of Severe Therapy yes Add Alternate Inhibitors Hypoglycemia Agent⁵ $$ no
Add Sulfonylureas ⁴ Contraindications: DPP-4 Inhibitor Severe sulfa allergy $$$$ →Use Glipizide 5 mg: ½ tablet bid → Meglintinides 1 tablet bid → 2 tablets bid Titrate q. 2 weeks until at target SGLT-2 Inhibitor $$$$ Add Basal Long After 3 Acting Insulin At Goal A1c ≥ 1% no months of Goal or Alternate Agent⁵ GLP-1 Receptor Agonist yes $$$$
Add Basal Long Acting Insulin Maintain 10 units SQ at hs Therapy ↑ 2 units q. 2 days until at target
⁴ Carries increased risk of Hypoglycemia. Severe hypoglycemia = resulting or ¹ Excluding Pregnancy – for pregnant women and women intending pregnancy, use CDAPP likely to result in seizures, LOC, or needing help from others. Mild guidelines. hypoglycemia = recognized signs and symptoms or neuro-glycopenia (e.g. ² Individualize A1c goal based on risk of hypoglycemia, duration of DM, life expectancy, co- hunger or sweating) that the patient can effectively self-treat. morbidities, vascular complications, patient resources and support system. ⁵ Choice dependent on patient and disease-specific factors. Each new class of ³ Self Monitoring Blood Glucose targets: postprandial < 180mg/dL; bedtime 100-150 mg/dL. non-insulin agents lowers A1c ~ 1%. If A1c target is still not achieved after 3 months of dual therapy, proceed to three-drug combination. Medications for Management of Type 2 Diabetes
- t Medication / Maximum Optimal Caution/ side effects risk
Recommended Titration Cost eigh Hypo
W Dose Interval Efficacy Advantages glycemic
Biguanides 2,000mg daily 1-2 weeks Serum creatinine; repeat q 12 months , 2 or or - Do not use if HF class 3-4; LFTs>3xULN; or eGFR<30. metformin (500, 850, 1000mg)
/ event
1 2 ss Maximum dose 1000mg if eGFR 30-45 ER (500, 750, 1000mg) ow $ L Lo High
mono Increased risk GI side effects -> consider extended release therapy First line Neutral risk CVrisk oral agent
Long-term use associated with vitamin B12 deficiency Sulfonylureas (SU) 20mg twice 2 weeks Sulfa allergy
glipizide2 (2.5, 5, 10mg) daily Hypoglycemia line line - 2 Weight gain
1 D/C SU with initiation of insulin igh ain glyburide ER (2.5, 5, 10mg) $ risk H G microvascular
Combination Med / oral therapy Glyburide/metformin1, 2 (1.5- Dual,second 250mg, 2.5/5mg-500mg) High Thiazolidinediones (TZD) 45mg daily Heart failure 2 Edema pioglitazone (15, 30, 45mg) /
1 Increased fractures Combination Med $ Low Gain insulin 4 High Bladder cancer concerns
Pioglitazone/metformin sensitivity (15/500/850mg) Meglitinides (Glinide) 16mg daily / repaglinide2 (0.5,1, 2mg) 360mg daily
2
nateglinide (60,120mg) 1 $$ High Gain glucose
p A1C loweringA1C p Alpha-glucosidase inhibitors (AGI) 300mg 1-2 Often poorly tolerated acarbose2 (25,50, 100mg) months Modest efficacy (0.4-0.7% reduction A1C) miglitol2 (25,50, 100mg) Need to be dosed more than once/day $$ Effective in reducing PPG with high carb intake
DPP-4 Inhibitors 25mg daily Rare 3
Dual agent alternative therapy; alogliptin (6.25, 12.5, 25mg) 4
linagliptin4
1, 3 Low Combination Med $$$$ Neutral alogliptin/pioglitazone2 (12.5- 15/30/45, 25-15/30/45mg) Intermediate alogliptin/metformin2 (12.5- 500/1,000mg)
Medication c Maximum Optimal Caution/side effects
Risk Recommended Titration Dose Interval Weight Efficacy / Cost Advantages Hypoglycemi
SGLT-2 inhibitors 5mg daily genital mycotic infections canagliflozin4 Dehydration CV dapagliflozin4 Fracture risk empagliflozin4 Polyuria Combination Med LDL-C
canagliflozin/metformin, ay improve creatinine Low m 4 Loss $$$$ Invokamet Possible risk of lower-limb amputation with canagliflozin empagliflozin/metformin,
Synjardy4
4 BP
dapagliflozin/metformin, Xigduo empagliflozin/linagliptin, ; Glyxambi4 Intermediate/ risk GLP-1 R Agonist (SQ pen injector) 1.8mg daily GI side effects 3
liraglutide, Victoza 1.5mg daily Pancreatitis risk CV
dulaglutide4 Heart rate Low Loss $$$$
High/ High/ risk Long-acting Insulin, basal 10U SQ HS or 10-15%, Hypoglycemia; duration 18 - 26hrs
2
Insulin glargine, Basalgar , 0.1-0.2U/kg/d or 2-4U Training/monitoring requirements 4 ain Lantus $$$ 1-2x/wk - ighest G 4 $ H insulin detemir, Levemir Highest
Intermediate-acting Insulin, NPH Hypoglycemia; duration 16 - 24hrs
3
insulin isophane, HumulinN ,
NovolinN3
$$$ Gain Highest Highest Insulin
Short-acting Insulin Hypoglycemia; duration 5 - 8hrs
regular insulin, HumulinR3, $$$
3 4 - Gain
NovolinR , Afrezza (inhalation) $ Highest Highest
Fast-acting Insulin Hypoglycemia; duration 3 - 4hrs
3
insulin lispro, Humalog Monitor blood glucose before breakfast and before meals 2-
3 $
insulin aspart, Novolog Gain 4 times/day Highest insulin glulisine, Apidra3 Highest
1Generic available; 2Partnership Healthplan of California formulary; 3PHC formulary restrictions apply: quantity limit or step therapy – previous claims for metformin, a secondary formulary oral antidiabetic agent &/or basal insulin required (see formulary); 4PHC non-formulary – TAR required; 5PHC not available https://client.formularynavigator.com/Search.aspx?siteTestID=1196