1. 1 Core Defects of Type 2 Diabetes Targeting Mechanisms for a Comprehensive Approach 1 Part 4 of 4

2. 2 *Compared with placebo plus metformin. † In patients inadequately controlled on metformin monotherapy. ‡ Least-squares means adjusted for prior antihyperglycemic therapy status and baseline value. § Difference from placebo. n=453n=454 24-week placebo-adjusted results † –0.7% ‡ –25 ‡ n=387 –51 ‡ (95% CI: – 0.8, – 0.5)(95% CI: – 31, – 20)(95% CI: – 61, – 41) JANUMET™ (sitagliptin/metformin HCl) Label Data: Sitagliptin Plus Metformin Provided Significant Improvements in Glycemic Control Beyond Metformin Alone*

3. 3 JANUMET™ (sitagliptin/metformin HCl) Label Data: Percentage of Patients Achieving A1C <7.0% With the Combination of Sitagliptin and Metformin A total of 41 (of 224) patients on placebo plus metformin and 213 (of 453) patients on sitagliptin plus metformin achieved A1C <7.0%. Intent-to-treat population using last observation on study before pioglitzone rescue therapy. 47% 18% n=224 n=453 Percentage of patients Placebo + metformin Sitagliptin + metformin P<0.001 24-Week Study

4. 4 JANUMET™ (sitagliptin/metformin HCl) Label Data: Weight Change and Hypoglycemia Incidence in Patients Treated With the Combination of Sitagliptin and Metformin 24-Week Add-On Therapy to Metformin Study HypoglycemiaWeight Change

5. 5 JANUMET™ (sitagliptin/metformin HCl) Label Data: Overall Incidence of Selected Adverse Reactions in Patients Treated With the Combination of Sitagliptin and Metformin Overall: The incidence of side effects and discontinuation rates with sitagliptin and metformin were similar to those with placebo and metformin. The incidence of hypoglycemia in patients treated with sitagliptin and metformin was similar to that in patients treated with placebo and metformin (1.3% vs 2.1%). The incidence of gastrointestinal disturbances in patients treated with sitagliptin and metformin was similar to that in patients treated with placebo and metformin (11.6% vs 9.7%). The most common adverse experience in sitagliptin monotherapy reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo was nasopharyngitis. The most common (>5%) established adverse reactions due to initiation of metformin therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.

6. 6 JANUMET™ (sitagliptin/metformin HCl) Label Data: Incidence of Selected Gastrointestinal Adverse Reactions in Patients Treated With Sitagliptin and Metformin Other AEs Sitagliptin and Metformin, % Placebo and Metformin, % Nausea1.30.8 Vomiting1.10.8 Abdominal Pain2.23.8 Diarrhea2.42.5 Incidence in Patients With Sitagliptin or Placebo Added to a Twice-Daily Metformin Regimen

7. 7 JANUMET™ (sitagliptin/metformin HCl): Contraindications JANUMET is contraindicated in patients with: –Renal disease or renal dysfunction, eg, as suggested by serum creatinine levels ≥1.5 mg/dL (males), ≥1.4 mg/dL (females) or abnormal creatinine clearance –Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma JANUMET should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

8. 8 JANUMET™ (sitagliptin/metformin HCl): Selected Warnings and Precautions Metformin and sitagliptin are known to be substantially excreted by the kidney. The risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive JANUMET. Before initiation of therapy with JANUMET and at least annually thereafter, renal function should be assessed and verified as normal. Concomitant medication(s) that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion [see Drug Interactions (7.1)], should be used with caution.

9. 9 JANUMET™ (sitagliptin/metformin HCl): Selected Warnings and Precautions Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on JANUMET therapy, the drug should be promptly discontinued. Use of JANUMET should be temporarily suspended for periods of stress, trauma, infection, or any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal. Patients should be warned against excessive alcohol intake, acute or chronic, while receiving JANUMET. JANUMET should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Hematologic parameters should be measured annually.

10. 10 JANUMET™ (sitagliptin/metformin HCl): Drug Interactions Drug Interactions –Pharmacokinetic drug interaction studies with JANUMET have not been performed; however, such studies have been conducted with the individual components of JANUMET (sitagliptin and metformin hydrochloride). –Use cationic drugs with caution. –There are no known clinically meaningful drug interactions for sitagliptin. Use of Metformin With Other Drugs –When drugs that tend to produce hyperglycemia are administered to a patient receiving JANUMET, the patient should be closely monitored to maintain adequate glycemic control.

11. 11 JANUMET™ (sitagliptin/metformin HCl): Recommended Dosing In general: twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal side effects due to metformin Starting dose based on patient’s current regimen Available dosage forms: –50 mg sitagliptin/500 mg metformin –50 mg sitagliptin/1,000 mg metformin Patients inadequately controlled on metformin: –Starting dose equal to 100 mg sitagliptin daily plus current metformin dose Patients inadequately controlled on sitagliptin: –Starting dose 50 mg sitagliptin/500 mg metformin twice daily –Titrated up to 50 mg sitagliptin/1,000 mg metformin twice daily Patients switching from sitagliptin coadministered with metformin: –Initiate at current doses of sitagliptin and metformin Tablets not shown at actual size.

12. 12 A1C, % Treatment: Metformin initiated Patient History: 45-year-old woman, bus driver BMI = 31 kg/m 2 Borderline hypertension Type 2 diabetes diagnosed Lab Results: A1C = 7.6% FPG = 150 mg/dL Serum creatinine = 0.9 mg/dL (CrCl = 104 mL/min) Treatment: Diet and exercise recommended Lab Results: A1C = 8.0% FPG = 170 mg/dL Serum creatinine = 1.0 mg/dL (CrCl = 100 mL/min) Treatment: Metformin up-titrated to 2,000 mg/day Case Study: Caroline D. Considerations for next treatment decision: Mechanism of action Efficacy Tolerability Current Lab Results: A1C = 7.7% FPG = 150 mg/dL

13. 13 Overall Summary A majority of patients with type 2 diabetes may fail to attain A1C goal with the conventional treatment paradigm The components of JANUMET™ (sitagliptin/metformin HCl) have complementary MOAs and comprehensively address 3 core pathophysiologic defects of type 2 diabetes. Coadministration of sitagliptin and metformin results in: –Significant reductions in A1C, FPG, and PPG compared with metformin alone –Weight loss comparable to metformin alone –Low incidence of hypoglycemia comparable to metformin alone –Similar overall incidence of side effects to metformin alone