1. Assistant Professor of Clinical Pharmacy
Diabetes Mellitus
Ibrahim Sales, Pharm.D.
Assistant Professor of Clinical Pharmacy
King Saud University

2. Non-pharmacologic Therapy
Diet
Medical nutrition therapy is recommended for all persons with DM
Physical activity
Aerobic exercise
Goal: at least 150 minutes/week of moderate (50%–70% maximal heart rate) intensity exercise
Resistance training at least twice weekly

3. Benefits of Modest Weight Loss in Type 2 DM
Loss of 20lb (10%) in obese subjects reduced FBG by 29mg/dL and A1C by 1.1%
Loss of 10lb (5%) reduced DBP by 5%
Loss of 6lb (3%) in obese men decreased
Total cholesterol by 17%
LDL-C by 9%
Triglycerides by 35%
Arch Intern Med. 1987;147:1748
Diabet Med. 1990;7:228
Arch Intern Med. 1997;157:169
Metabolism. 1999;5:641

4. Medical Nutrition Therapy in Type 2 DM Management

5. Oral Medications

6. Mechanisms of Action of Oral DM Medications

7. Biguanide Suppression of basal hepatic glucose production
Enhancement of peripheral (muscle) tissue insulin sensitivity
increases uptake of glucose in tissues
No direct effect on β cells
Generic Name
Dose (mg)
Recommended Starting Dosage (mg/day) 
Maximum Dose (mg/day) 
Duration of Action 
Metabolism or Therapeutic Notes 
Nonelderly 
Elderly 
Metformin
500, 850, 1,000
500 mg twice a day
Assess renal function
2,550
Up to 24 hours
No metabolism; renally secreted and excreted
Metformin extended- release
500, 750, 1,000
500–1,000 mg with evening meal
Take with evening meal or may split dose; can consider trial if intolerant to immediate-release
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:

8. Biguanide Most common adverse effects: GI Weight loss can occur
abdominal discomfort, stomach upset, diarrhea
Weight loss can occur
anorexia
stomach fullness

9. Biguanide Contraindications
High risk patients for lactic acidosis
CHF, hypoxic states, shock, septicemia, severe liver disease, alcohol use
Renal insufficiency
SCr ≥ 1.4 mg/dL in women
SCr ≥ 1.5 mg/dL in men
Intravenous dye procedures
risk of acute renal failure
withhold the day of procedure
may restart 2 to 3 days post-procedure

10. Biguanide Average HbA1c reduction: 1.5 to 2.0%
FBG reduction: 60 to 80 mg/dL
Reduce FBG levels when > 300 mg/dL
Decrease plasma triglycerides & LDL-C by ~8 to 15%
Increases HDL-C: 2%

11. Biguanide Weight loss: 2 to 3 kg Use in all type 2 DM patients
If tolerated & not contraindicated
Only oral antidiabetic agent proven to reduce mortality risk
UKPDS shows metformin is best suited for obese type 2 DM patients; reduces mortality

12. Biguanide Summary Medication (A1C reduction) Mechanism of Action
Comments
Metformin
(1.5% to 2%)
Decreases hepatic glucose production
Improves insulin sensitivity (Increases peripheral glucose uptake and utilization)
Decreases intestinal absorption of glucose
Modest weight loss is common
Contraindicated in patients with renal impairment (CrCl < 60 mL/min)
Gastrointestinal side effects are most common
Low risk of hypoglycemia

13. Case 2: Medication-Induced Hypoglycemia
TY is a 44 y/o male with Type 2 DM. This is his first visit with you. He is only taking Metformin 1000mg twice daily. Last week he was exercising and halfway through, he stopped because he was feeling extremely weak and was sweating profusely. He took his blood glucose and it was 68. He wants to know if this is a common symptom because of his medication.

14. Sulfonylureas Enhance insulin secretion
bind SUR receptors on pancreatic β cells
results in suppressed hepatic glucose production
Classification: 1st & 2nd generation
differences in potency, adverse effects
no therapeutic superiority among agents
Glyburide
requires adjustment for renal dysfunction; higher risk of hypoglycemia

15. Sulfonylureas
Type 2 DM
Sulfonylurea
Insulin Effect
B L D HS B

16. Recommended Starting Dosage (mg/day) Equivalent Therapeutic Dose (mg)
Sulfonylureas
Generic Name
Dose (mg)
Recommended Starting Dosage (mg/day) 
Equivalent Therapeutic Dose (mg) 
Maximum Dose (mg/day) 
Duration of Action 
Metabolism or Therapeutic Notes 
Nonelderly
Elderly 
1st Generation
Acetohexamide
250, 500
250
125–250
500
1,500
Up to 16 hours
Metabolized in liver; metabolite potency equal to parent compound; renally eliminated
Chlorpropamide
100, 250
100
Up to 72 hours
Metabolized in liver; also excreted unchanged renally
Tolazamide
100, 250, 500
100–250
1,000
Up to 24 hours
Metabolized in liver; metabolite less active than parent compound; renally eliminated
Tolbutamide
1,000–2,000
500–1,000
3,000
Up to 12 hours
Metabolized in liver to inactive metabolites that are renally excreted
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:

17. Recommended Starting Dosage (mg/day) Equivalent Therapeutic Dose (mg)
Sulfonylureas
Generic Name
Dose (mg)
Recommended Starting Dosage (mg/day) 
Equivalent Therapeutic Dose (mg) 
Maximum Dose (mg/day) 
Duration of Action 
Metabolism or Therapeutic Notes 
Nonelderly
Elderly 
2nd Generation
Glipizide
5, 10 5
2.5–5 40
Up to 20 hours
Metabolized in liver to inactive metabolites
2.5, 5, 10, 20 20
24 hours
Slow-release form; do not cut tablet
Glyburide
1.25, 2.5, 5
1.25–2.5
Up to 24 hours
Metabolized in liver; elimination ½ renal, ½ feces
Glyburide, micronized
1.5, 3, 6 3
1.5–3 12
Equal control, but better absorption from micronized preparation
Glimepiride
1, 2, 4
1–2
0.5–1 2 8
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:

18. Sulfonylureas Most common side effect: hypoglycemia
Higher with chlorpropamide & glyburide
High risk patients require lower doses
elderly
renal/hepatic disease
patients that skip meals
vigorous exercise
substantial weight loss
Weight gain also common (~3kg)
Less common adverse effects: rash, GI upset

19. Sulfonylureas Titrate sulfonylureas doses every 1 to 2 weeks
Maximal effective dose ~60 to 75% stated max dose
At equipotent doses, all sulfonylureas equally effective at lowering blood glucose

20. Sulfonylureas Average HbA1c reduction: 1.5 to 2%
FBG reduction: 60 to 70 mg/dL
Most patients do not reach glycemic goal with monotherapy
1˚ failure: < 30 mg/dL drop in FBG
low C-peptide
high (> 250 mg/dL) FBG
2˚failure: good initial response, but insufficient to reach or maintain glycemic goal
5 to 7% per year failure rate

21. Sulfonylureas Summary
Medication
(A1C reduction)
Mechanism of Action
Comments
Glyburide; Glibenclamide
Glipizide
Glimepiride
Gliclazide
(1.5% to 2%)
Stimulates insulin release from the β-cells of the pancreas
May cause weight gain
High propensity for hypoglycemic episodes

22. Recommended Starting Dosage (mg/day)
Meglitinides
Stimulate insulin secretion from pancreatic β cells
require presence of glucose
Similar mechanism to sulfonylureas
faster onset, shorter duration
Generic Name
Dose (mg)
Recommended Starting Dosage (mg/day) 
Maximum Dose (mg/day) 
Duration of Action 
Metabolism or Therapeutic Notes 
Nonelderly
Elderly 
Nateglinide
60, 120
120 with meals
120 mg three times a day
Up to 4 hours
Metabolized by cytochrome P450 (CYP450), CYP2C9, and CYP3A4 to weakly active metabolites; renally eliminated
Repaglinide
0.5, 1, 2
0.5–1 with meals 16
Metabolized by CYP3A4 to inactive metabolites; excreted in bile
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:

23. Meglitinides
Type 2 DM
Meglitinide
Insulin Effect
B L D HS B

24. Meglitinides Most common adverse effect: hypoglycemia
less than with sulfonylureas
Weight gain may occur
repaglinide: 2 to 3 kg
nateglinide: < 1 kg
CYP3A4 inducers or inhibitors may interact with repaglinide
May use in patients with renal insufficiency
Use with caution in severe hepatic impairment

25. Meglitinides
May be used as monotherapy or in combination with metformin or TZDs in Type 2 DM
Dose up to 30 min prior to each meal
dose can be skipped if a meal is skipped
meals low in carbohydrates may not need a dose
Average HbA1c reduction < 1%
Reduces FBG by ~60mg/dL
Useful in reducing postprandial glucose excursions in patients close to glycemic goals
Patients having a poor response to sulfonylurea therapy are not likely to respond if these drugs are added

26. Repaglinide vs. Nateglinide Monotherapy
Diabetes Care 2004;27:

27. Meglitinides Summary Medication (A1C reduction) Mechanism of Action
Comments
Repaglinide
Nateglinide
(0.5% to 1%)
Stimulates the release of insulin from the β-cells of the pancreas
Shorter acting than the SUs
Taken with meals
The dose should be skipped if the meal is skipped
Lower risk of hypoglycemia than with SUs
May cause weight gain

28. α-Glucosidase Inhibitors
Competitively inhibit enzymes in the small intestine
delay sucrose & complex carbohydrate breakdown
Absorption of glucose is delayed to the distal portion of the small intestine resulting in a reduction of “peak” postprandial blood glucose concentrations
Reduce postprandial hyperglycemia
Generic Name
Dose (mg)
Recommended Starting Dosage (mg/day) 
Maximum Dose (mg/day) 
Duration of Action 
Metabolism or Therapeutic Notes 
Nonelderly 
Elderly 
Acarbose
25, 50, 100
25 mg one to three times a day
25–100 mg three times a day
1–3 hours
Eliminated in bile
Miglitol
Eliminated renally
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:

29. α-Glucosidase Inhibitors
Without Pharmacotherapy
With Pharmacotherapy

30. α-Glucosidase Inhibitors

31. α-Glucosidase Inhibitors
Adverse effect:
GI side effects most common
flatulence, bloating, abdominal discomfort, diarrhea
May elevate serum aminotransferase
Contraindications:
IBD
colonic ulceration
intestinal obstruction
cirrhosis

32. α-Glucosidase Inhibitors
Efficacy
Reduce postprandial glucose 40 to 50 mg/dL
FBG relatively unchanged (~10% reduction)
Average HbA1c reduction: 0.3 to 1%
Beneficial in patients close to target HbA1c with near-normal FBG but high postprandial levels
Do not affect the absorption of simple sugars such as glucose and lactose

33. α-Glucosidase Inhibitor
May be monotherapy or used with metformin, sulfonylureas, insulin
Initiate with very low dose
25 mg with one meal a day
Increase gradually to maximum dose
50 mg TID patients ≤ 60 kg
100 mg TID patients > 60 kg
Take with 1st bite of a meal

34. Alpha-glucosidase Inhibitors
Medication
(A1C reduction)
Mechanism of Action
Comments
Acarbose
Miglitol
(0.3% to 1%)
Delays the breakdown of complex carbohydrates into glucose
The absorption of glucose is delayed in the distal portion of the small intestine
Can cause flatulence, abdominal pain, diarrhea
Not as effective as the other oral agents
Considered 2nd or 3rd line therapy

35. TZDs: Thiazolidinediones
May be used in type 2 DM therapy
Enhance insulin sensitivity at muscle, liver, fat tissues
Decrease hepatic glucose production
Requires presence of insulin
Generic Name
Dose (mg)
Recommended Starting Dosage (mg/day) 
Maximum Dose (mg/day) 
Duration of Action 
Metabolism or Therapeutic Notes 
Nonelderly 
Elderly 
Pioglitazone
15, 30, 45 15 45
24 hours
Metabolized by CYP2C8 and CYP3A4; two metabolites have longer half-lives than parent compound
Rosiglitazone
2, 4, 8
2–4 2
8 mg/day or 4 mg twice a day
Metabolized by CYP2C8 and CYP2C9 to inactive metabolites that are renally excreted
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:

36. Thiazolidinediones Usual reduction in HbA1c of 1.5% - 2.5%
Decreases in blood glucose can be seen within 2-4 weeks
Maximum glucose lowering effects may take up to 12 weeks
Demonstrated perseverance of effect for up to 1-2 years

37. TZD Adverse Effects May increase ALT Fluid retention
CI if ALT > 2.5 times upper limit of normal (ULN)
Discontinue if ALT > 3 times ULN
Troglitazone (1st approved TZD) removed from market in 2000 due to deaths from liver failure
Fluid retention
Edema, dilutional anemia, pulmonary edema, HF
CI in NYHA Class III & IV
Black box warning for heart failure

38. TZD Adverse Effects Weight Gain Increased fracture risk Ovulation
1.5 to 6 kg
Fluid retention & fat accumulation
Increased fracture risk
upper & lower limbs of postmenopausal women
Ovulation
aovulatory patients can resume ovulation
pregnancy & contraception precautions required
pregnancy category C

39. TZDs Average HbA1c reduction ~1.5%
FBG reduction: 60 to 70 mg/dL at max doses
Maximal glycemic-lowering effects after 3 to 4 months
Triglycerides:
pioglitazone: 10 to 20% decrease
rosiglitazone: neutral effect
LDL:
pioglitazone: no significant increase
rosiglitazone: 5 to 15% increase
HDL: both increase 3 to 9 mg/dL 39

40. Thiazolidinediones Summary
Medication
(A1C reduction)
Mechanism of Action
Comments
Rosiglitazone
Pioglitazone
(1.5% to 2.5%)
Improves insulin sensitivity in skeletal muscle and adipose tissue
Decreases hepatic glucose output
FDA-imposed restricted use of rosiglitazone due to cardiovascular ischemic risk
Risk of bladder cancer with pioglitazone
Long onset and prolonged effects after discontinuation
Can cause weight gain, edema, and worsen CHF

41. “Incretin Effect”
Plasma Insulin Responses to Oral and Intravenous Glucose
Normal Weight: Non-Diabetic Subjects
Normal Weight: Diabetic Subjects 90 90
Oral Glucose
Intravenous Glucose
Oral Glucose
Intravenous Glucose 60 60
Plasma Insulin (U/mL)
Plasma Insulin (U/mL) 30 30 30 60 90
120
150
180 30 60 90
120
150
180
Time (min)
Time (min)
Non-Diabetic Subjects (glucose range mmol/L) Diabetic Subjects (glucose range mmol/L)
Data from: Perley M, et al. J Clin Invest 1967; 46:

42. Incretins
Peptide hormones secreted by enteroendocrine cells in the GI tract
Modulate pancreatic islet secretions
Other effects on nutrient homeostasis
Two major incretins that affect glucose metabolism
GLP-1: glucagon-like peptide-1
GIP: glucose-dependent insulinotropic polypeptide

43. GLP-1
Produced by intestinal L-cells, which are located predominately in the ileum and colon (distal portion of the gut)
Potent insulinotropic hormone
Plasma levels increase rapidly in response to meals (carbohydrate & lipid)
Once secreted it is rapidly inactivated by dipeptidyl peptidase IV (DPP-IV) t1/2 ~ 2 min
Type 2 DM & Impaired Glucose Tolerance (IGT) present with lower plasma GLP-1 compared to healthy controls

44. GLP-1 Secretion and Metabolism
Inactive
Mixed Meal
DPP-IV
Intestinal GLP-1 Release
GLP-1 (7-36)
Active
Rapid Inactivation
(>80% of pool)
Plasma
GLP-1 Actions
Renal Clearance
DPP-IV = Dipeptidyl peptidase-IV
Deacon CF, et al. Diabetes ;44:

45. GLP-1 Modes of Action in Humans
Upon ingestion of food…
Stimulates glucose- dependent insulin secretion
Suppresses glucagon secretion
Slows gastric emptying
GLP-1 is secreted
from the L-cells
in the intestine
Reduces food intake
Long term effects demonstrated in animals…
This in turn…
Increases beta-cell mass and maintains beta-cell efficiency
Drucker DJ. Curr Pharm Des 2001; 7: Drucker DJ. Mol Endocrinol 2003; 17:

46. Strategies to Enhance Incretin Action in Diabetes
Glucagon-like peptide-1 (GLP-1) analogues*
Exenatide (synthetic Exendin-4)*
Dipeptidyl peptidase-IV (DPP-IV) inhibitors
* Incretin mimetic agents

47. DPP-IV Inhibitors GLP-1(9-36) Inactive Mixed Meal Plasma
Intestinal GLP-1 Release
GLP-1 (7-36)
Active
Rapid Inactivation
(>80% of pool)
Plasma
↑ Activity
Incretin Enhancement
GLP-1 Actions
Renal Clearance
DPP-IV = Dipeptidyl peptidase-IV
Deacon CF, et al. Diabetes ;44:

48. DPP-IV Inhibitors Inhibit DPP-IV which degrades GLP-1
prolongs GLP-1 t½
GLP-1 deficient in type 2 DM
Partially reduces elevated postprandial glucagon
Stimulates glucose-dependent insulin secretion

49. DPP-IV Inhibitors May be used as monotherapy or in combination therapy
Average HbA1c reduction 0.7 to 1.0%
Mild hypoglycemia may occur
Postmarking reports of serious hypersensitivity reactions
anaphylaxis
angioedema
exfoliative skin conditions (Stevens-Johnson syndrome)

50. Dipeptidyl peptidase-4 (DPP-4) Inhibitors Summary
Medication
(A1C reduction)
Mechanism of Action
Comments
Linagliptin
Saxagliptin
Sitagliptin
Vildagliptin
(0.7% to 1%)
Inhibits the degradation of endogenous incretins which increases insulin secretion
Decreases glucagon secretion
Weight neutral
Rare instances of hypoglycemia
Considered 2nd line therapy
Reports of acute pancreatitis

51. Non-insulin Injectable Medications

52. Exendin-4 in the Gila Monster
Exendin-4 was originally isolated from the salivary secretions of the Gila monster
Exendin-4 was subsequently found to circulate as a meal-related peptide in this animal
Exendin-4 has possible endocrine function in the lizard Heloderma suspectum (Gila monster)
400000
4 mice
1 rat
300000
Plasma Exendin-4 Concentration (pg/mL)
200000
100000 3 6 9 12
Time After Meal (h)
Data from: Young AA. Glucagon-like peptide-1, exendin and insulin sensitivity. In Hansen B, Shafrir E,
Editors. Insulin Resistance and Insulin Resistance Syndrome. 1st ed. Harwood Academic Press; 2002,

53. Exenatide: Clinical Pharmacology
Dosage:
5 μg BID within a 60-minute period before the morning and evening meals
Based on clinical response dosage may be increased to 10 μg BID after 1 month of therapy
Adverse Effects:
Nausea
Jittery
Dyspepsia
Vomiting
Dizziness
Hypoglycemia
(with sulfyl use)
Diarrhea
Headache
Weight Loss
Storage:
Exenatide should be refrigerated (at all times) at 36º F to 46º F, protected from light
Pen should be discarded 30 days after first use, even if some drug remains in the pen

54. Exenatide Average HbA1c reduction ~0.9%
Significantly decreases postprandial glucose excursions
Modest effects on FBG
Average weight loss in studies: 1 to 2 kg over 30 weeks
long-term, open-labeled trials show continued weight loss for at least 2.5 years with 10 mcg BID dose
Improvements in triglycerides & HDL seen with exenatide 10 mcg BID 54

55. Nausea Is Dose-dependent and
Decreases Over Time 5 10 15 20 25 30
0-4
>4-8
>8-12
>12-16
>16-20
>20-24
>24-28
>28
Treatment (wk)
Incidence of Nausea
(% ITT Subjects)
10 µg
5 µg
Placebo
Buse JB, et al. Diabetes Care. 2004;27:

56. Effect of Exenatide on Body Weight
Buse JB, et al. Diabetes Care. 2004;27:

57. Plasma glucose (mmol/l)
Once-daily injection of Liraglutide covers 24-h BG profile in type 2 diabetes
Placebo 14
Liraglutide (6 µg/kg OD) 12
24-h glucose AUC
(mmol/l/h, mean ± SE)
232.3 ± 21.9
187.5 ± (p = 0.01) 10
Plasma glucose (mmol/l) 8 6
n=13 4 8 12 16 20 24
Time after injection (hours)
Injection (08.00)
Adapted from: Degn et al. Diabetes 2004;53:

58. Liraglutide Effect on FBG and Weight
Fasting serum glucose % mM
Weight change
Key observations:
Observations from liraglutide and metformin versus metformin and a sulfonylurea
Effect observed in the absence of hypoglycaemia
1mM = 20 mg/dL 1 -1 -2 -3 -1 -2 -3 -4
Liraglutide and metformin
Glimepiride and metformin
p<0.0001
p<0.015

59. Liraglutide: Effect on Weight
Continuing weight loss 2
Liraglutide and metformin 1
Glimepiride and metformin
Mean change in body weight from baseline (%) -1 -2 -3 1 2 3 4 5
Time (weeks)
Note: Data from the double-blind, double-dummy, randomised, parallel group dose titration phase 2 study including a total of 144 patients with an average HbA1c of %. All changes are from baseline; that is, FSG of mM and an average weight of kg.

60. Summary A 24-hour pharmacodynamic profile
Once-daily injection due to 12 hr half-life
Multiple anti-diabetic actions
Increases insulin and lowers glucagon secretion
Rapid and sustained glycaemic effect
Weight control
-cell mass increased in animal models
-cell function improved in type 2 diabetes
Strictly glucose-dependent actions
Very low hypoglycemia risk (no major and few minor events)
Counter-regulatory response to hypoglycaemia not impaired
Well-tolerated
Mild, transient GI-symptoms; no antibodies (12-week data)

61. Glucagon-like, peptide-1 (GLP-1) Mimetic
Medication
(A1C reduction)
Mechanism of Action
Comments
Exenatide
Exenatide weekly
Liraglutide
(1% to 1.5%)
Stimulates GLP-1 receptors which increases production of insulin in response to high blood glucose levels
Inhibits post-prandial glucagon release
Slows gastric emptying
Injections
Promotes weight loss
Nausea and diarrhea are common
Induces satiety

62. Pramlintide Adjunctive therapy for patients using insulin
Synthetic analog of amylin
neurohormone co-secreted from β-cells with insulin
Suppresses postprandial glucagon secretion
Reduces food intake
Slows gastric emptying

63. Pramlintide Subcutaneous injection in abdomen or thigh
variable absorption with arm injection
Adverse effects:
GI most common
nausea, vomiting, anorexia
may decrease over time
dose-related, slowly titrate dose upwards
May delay absorption of other medications; slow gastric emptying

64. Pramlintide
Reduce preprandial insulin dose 30 to 50% at pramlintide initiation
Basal insulin dose may be reduced if FBG close to goal
Dosing
Type 2: 60 to 120 mcg prior to meals
Type 1: 15 to 60 mcg prior to meals
2.5 units on 100 units/ml insulin syringe = 15 mcg of pramlinitide

65. Pramlintide Average HbA1c reduction 0.4 to 0.6%
Decreases prandial glucose excursions
Little effect of FBG concentrations
Main advantage in type 1 DM is that it stabilizes wide postprandial glycemic swings
Average weight loss in controlled trials: 1 to 2 kg

66. Warnings and Precautions

67. Case 3: Non-Insulin Injectables
YO is a 52 y/o female with Type 2 DM and central obesity. She was recently started on liraglutide and is now taking 1.8mg daily. She is nauseous after eating and states that this occurs even with her favorite #1 and #3 meal combos from McDonalds. She states that she knows that her diet is not good. How do you respond?

68. Treatment Algorithm 1st Agent 2nd Agent 3rd Agent Metformin SU
TZD or DDP-4 or GLP-1 or insulin
TZD
SU or DPP-4 or GLP-1 or insulin
DPP-4 inhibitor
SU or TZD or insulin
GLP-1 agonist
Insulin (usu. Basal)
TZD or DPP-4 or GLP-1
Treatment Algorithm

69. Add-Ona Dual Therapy: Average HbA1c Reduction
Drug Combination 
Change in HbA1c (%) 
Number of Studies 
Number of Subjects 
Sulfonylurea + metformin
–2.2 8
458
Sulfonylurea + insulin
–1.9 17 88
Meglitinide + thiazolidinedione
–1.7 1
434
Metformin + insulin
138
Sulfonylurea + α-glucosidase inhibitor
–1.6 3
177
Metformin + meglitinide
–1.4
226
Insulin + α-glucosidase inhibitor
–1.2 20
Insulin + thiazolidinedione 7
850
Sulfonylurea + thiazolidinedione
–1.1 12
1,315
Metformin + exenatide
–0.8 2
1,070
Metformin + vildagliptin
–0.7
416
Metformin + thiazolidinedione
–0.9
284
Metformin + α-glucosidase inhibitor
–0.4
173
aReductions are averages and do not imply superiority or inferiority of a combination.

70. Medication-specific Therapy
High HbA1C, High FBG
High HbA1C, Goal FBG, High PPBG
FASTING/BASAL
POST-PRANDIAL
Metformin
TZDs
Sulfonylureas
NPH Insulin
Long-acting insulins
Liraglutide
Glinides
Α-glucosidase inhibitors
Colesevelam
DPP-4 inhibitors
Incretin mimetics
(exenatide > liraglutide)
Fast/rapid acting insulins
Pramlintide

71. Assistant Professor of Clinical Pharmacy
Diabetes Mellitus
Ibrahim Sales, Pharm.D.
Assistant Professor of Clinical Pharmacy
King Saud University