1. Medications Used in the Treatment of Diabetes Mellitus
Kelly Green Boesen, Pharm D, BCPS, CDE

2. Type 1 DM Treatment Insulin!
Best results is to mimic normal physiology as close as possible
Long acting insulin, meal-time coverage with rapid acting insulin
Insulin pump therapy
Testing
Type 1 DM Treatment

3. Type 2 DM Treatment First line therapy often metformin
+/- sulfonylureas
+/- TZD
+/- DPP-4 inhibitor
+/- GLP-1 agonist
+/- basal insulin
Addition of other agents based on response
Combinations that are not optimal:
Sulfonylureas and meglitinides (same basic mechanism of action)
GLP-1 agonist and DPP-4 inhibitors (work on same pathway, GLP-1 agonists work better at this pathway)
Sulfonylureas and rapid acting insulin
Over 3 oral medications and not at goal
Type 2 DM Treatment

4. Antihyperglycemic therapy in type 2 diabetes: general recommendations (15).
Antihyperglycemic therapy in type 2 diabetes: general recommendations (15). The order in the chart was determined by historical availability and the route of administration, with injectables to the right; it is not meant to denote any specific preference. Potential sequences of antihyperglycemic therapy for patients with type 2 diabetes are displayed, with the usual transition moving vertically from top to bottom (although horizontal movement within therapy stages is also possible, depending on the circumstances). DPP-4-i, DPP-4 inhibitor; fxs, fractures; GI, gastrointestinal; GLP-1-RA, GLP-1 receptor agonist; GU, genitourinary; HF, heart failure; Hypo, hypoglycemia; SGLT2-i, SGLT2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione. *See ref. 15 for description of efficacy categorization. †Consider starting at this stage when A1C is ≥9%. ‡Consider starting at this stage when blood glucose is ≥300–350 mg/dL (16.7–19.4 mmol/L) and/or A1C is ≥10–12%, especially if symptomatic or catabolic features are present, in which case basal insulin + mealtime insulin is the preferred initial regimen. §Usually a basal insulin (NPH, glargine, detemir, degludec). Adapted with permission from Inzucchi et al. (15).
American Diabetes Association Dia Care 2015;38:S41-S48
©2015 by American Diabetes Association

5. Approach to starting and adjusting insulin in type 2 diabetes (15).
Approach to starting and adjusting insulin in type 2 diabetes (15). FBG, fasting blood glucose; GLP-1-RA, GLP-1 receptor agonist; hypo, hypoglycemia; mod., moderate; PPG, postprandial glucose; #, number. Adapted with permission from Inzucchi et al. (15).
American Diabetes Association Dia Care 2015;38:S41-S48
©2015 by American Diabetes Association

6. Type 2 DM Treatment Insulin therapy usually added to oral medications
Usually continue metformin to help with resistance
Usually add basal insulin first
If patients have high resistance, will see insulin dosing over 50 units/day
No maximal dosing on insulin
Insulin causes weight gain
Many patients will need insulin therapy at some point
Type 2 DM Treatment

7. Hypoglycemia Known to cause: Possibly when used with above:
Insulin
Sulfonylureas (Glipizide, Glyburide)
Meglitinides (Nateglinide, Repaglinide)
Possibly when used with above:
DPP-4 inhibitors (Alogliptin, Linagliptin, Sitagliptin, Saxagliptin)
GLP-1 Agonists (Exenatide, Liraglutide, Albiglutide)
May be precipitated with taking medications and skipping meals
Hypoglycemia

8. Insulin Principals Basal/bolus
Combination of long acting/rapid acting insulin to achieve as close to normal physiology
Insulin Principals

9. Insulin Principals

10. Rapid-Acting Insulin Lispro (Humalog) Aspart (Novolog)
Glulisine (Apidra)
Onset: 5-15 minutes
Peak: minutes
Duration of effect: 2-4 hours
Meal-time coverage, typically used in combination with long acting, sometimes used to reduce a high blood sugar outside of meal-times.
Can be dosed 15 minutes prior to a meal or within 15 of eating a meal.
Rapid-Acting Insulin

11. Short-Acting Regular (R) (Humulin R or Novolin R)
Onset: 30 minutes-1 hour
Peak: 2-4 hours
Duration: 5-8 hours
Meal-time coverage, typically used in combination with long acting, sometimes used to reduce a high blood sugar outside of meal-times.
Dosed 30 minutes before a meal.
Short-Acting

12. Intermediate-Acting NPH (N) (Humulin N, Novolin N, isophane)
Onset: 2 hours
Peak: hours
Duration: hours
Used to cover basal needs, often used in combination with short or rapid acting insulin
Intermediate-Acting

13. Type of Insulin / Brand Name
Onset
Peak
Duration
Reason
LONG-ACTING
Insulin glargine (Lantus)
2 hours
No peak
20-24 hr
Covers basal insulin needs up to 24 hours, often used in combination with rapid acting insulin.
Insulin detemir (Levemir)
3-9 hours
Up to 24h
Long-Acting

14. Pre-mixed (SA: short-acting, IA: intermediate-acting)
Humulin 70/30
Novolin 70/30
Onset: SA: 30 minutes, IA: 2 hours
Peak: SA: 2-4 hours, IA: 4-12 hours
Duration: SA: 5-8 hours, IA: hours
70% of the dose is NPH, 30% of the dose is regular
Pre-mixed (SA: short-acting, IA: intermediate-acting)

15. Pre-mixed (SA: short-acting, IA: intermediate-acting)
Novolog 70/30
Humalog 70/30
Onset: SA: 5-15 minutes, IA: 2 hours
Peak: SA: minutes, IA: 4-12 hours
Duration: SA: 2-4 hours, IA: hours
70% of the dose is intermediate acting, 30% of the dose is rapid acting
Pre-mixed (SA: short-acting, IA: intermediate-acting)

16. Pre-mix Other combination products
First number is intermediate acting, second is fast acting.
Usually dosed twice daily prior to am and pm meal
Humulin/Novolin products use regular as the fast-acting.
Dosing occurs 30 minutes before the meal.
Humalog/Novolog use a rapid-acting.
Dosing occurs 5-15 minutes before meal.
Pre-mix

17. Evaluating Insulin Efficacy
Fasting glucose readings are reflective of basal insulin coverage
Pre-lunch, Pre-dinner, Pre-bedtime readings reflect how well the previous meal-time was covered with short acting insulin
2-hour post prandial readings reflect meal-time coverage
Evaluating Insulin Efficacy

18. Type 2: Other DM Medications
Sulfonylureas
Biguanides
Meglitinides
Thiazolidinediones (TZD)
Dipeptidyl pepsidase-4 inhibitors (DPP-4 inhibitors)
GLP-1 agonists
Alpha-Glucosidase Inhibitors
Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors
Type 2: Other DM Medications

19. Sulfonylureas Glipizide (Glucotrol®), Glyburide (Micornase®)
Increases insulin secretion from pancreatic beta cells, usually in response to food intake
A1c reduction of 1-2%
Some controversy over causing increased CV risk, acceleration of beta cell destruction
First began using for treatment in the 1950’s
Possible weight gain
Sulfonylureas

20. Sulfonylureas Should see overall blood glucose numbers decreasing
Full effect takes about 7 to 10 days to see
When adding basal insulin, this is sort of like meal-time coverage
Sulfonylureas

21. Biguanides Metformin (Glucophage®) Not a hypoglycemic agent
Decreases hepatic gluconeogenesis
Decreases intestinal absorption of glucose
Improve insulin sensitivity in skeletal muscle
Possible weight loss
Should see overall lowering of blood glucose
A1c reduction of 1-2%
Biguanides

22. Biguanides Monitoring
Periodic renal function
Needs to be dose adjusted or stopped for renal impairment
GI side effects are the most common, can be alleviated with slow titration
Must be stopped for 48 hours after any scan if contrast given
Biguanides

23. Meglitinides Nateglinide (Starlix®), Repaglinide (Prandin®)
Short acting insulin secetragogues, stimulates insulin release from pancreatic beta cells
Dosed 3 times a day with the meal
Drug interactions
Meal-time coverage
A1c reduction of %
Meglitinides

24. Thiazolidinediones (TZD)
Pioglitazone (Actos®), Rosiglitazone (Avandia®)
Not hypoglycemic
Improved insulin sensitivity of muscles
Cause fluid retention/swelling, contraindicated in heart failure
Require LFT monitoring
Not used as widely due to associated CV risk with
May take weeks to months for full effect
A1c reduction of %
Thiazolidinediones (TZD)

25. Dipeptidyl pepsidase-4 inhibitors (DPP-4 inhibitors)
Alogliptan (Nesina®), Linagliptin (Tradjenta®), Sitagliptan (Januvia®), Saxagliptin (Onglyza®)
Slows inactivation of incretin hormone (GLP-1), increases insulin release and decreases glucagon secretion
Results in lower circulating glucose
Weight neutral
A1c reduction %
Dipeptidyl pepsidase-4 inhibitors (DPP-4 inhibitors)

26. Dipeptidyl pepsidase-4 inhibitors (DPP-4 inhibitors)
Monitor renal function periodically
Side effects include:
Upper respiratory tract infections
Arthralgias
Dipeptidyl pepsidase-4 inhibitors (DPP-4 inhibitors)

27. Exenatide (Byetta®), Liraglutide (Victoza®), Albiglutide (Tanzeum®)
Increased insulin production and release when glucose is elevated
Slows gastric emptying
Weight loss, reduced food intake
Subcutaneous injection
A1c reduction %
GLP-1 agonists

28. GLP-1 agonists Warnings about pancreatitis
Most common side effects are GI related, can be alleviated with slow titration
GLP-1 agonists

29. Alpha-Glucosidase Inhibitors
Acarbose (Precose®), Miglitol (Glyset®)
Result in a reduction of carbohydrate absorption
Reduces post-prandial blood glucose elevation
Taken with each meal
GI side effects
Meal-time coverage
A1c reduction %
Alpha-Glucosidase Inhibitors

30. Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors
Canagliflozin (Invokana®), Dapagliflozin (Farxiga®), Empagliflozin (Jardiance®)
Blocks reabsorption of glucose in the kidneys to increase excretion through the urine
UTI’s, yeast infections, hyperkalemia, DKA
Possible weight loss
A1c reduction %
Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors

31. Other DM Treatment Daily aspirin therapy based on CV risk
Treatment of HTN (use of ACEI/ARBs for renal protection)
Treatment of Dyslipidemia
Statins
Fish oil
Possibly gemfibrozil
Neuropathy
TCA’s (amitriptyline, nortriptyline)
Gabapentin, Pregabalin (Lyrica®)
Narcotics??
Vaccines (influenza, pneumococcal, Hepatitis B)
Other DM Treatment