Initial Fixed-Dose Combination Therapy With JANUMET™ † (sitagliptin/metformin FDC) vs Metformin Monotherapy 079 Study – Phase A † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Study Objective Objective  To assess the efficacy, safety, and tolerability of initial therapy with sitagliptin/metformin FDC (JANUMET) compared with metformin alone in patients with type 2 diabetes and moderate to severe hyperglycemia on diet and exercise. 1,2 FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Study End Points Primary end points 1,2  Effect of sitagliptin/metformin FDC on mean HbA 1c compared with that of metformin at 18 weeks  Safety and tolerability of sitagliptin/metformin FDC Selected secondary end points 1,2  Change from baseline in HbA 1c (by mean and median baseline HbA 1c values), FPG, proinsulin-to-insulin ratio, and HOMA-β  Proportion of patients at HbA 1c goal (<7%) at 18 weeks FDC=fixed-dose combination; FPG=fasting plasma glucose; HOMA- β=homeostasis model assessment of beta-cell function. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Overall Disposition of Patients Screened (N=2042) Randomized (n=1250) Excluded (n=792) Sitagliptin/ metformin FDC (n=626) Discontinued (n=142) Adverse experience (n=23) Creatinine/CrCl criteria (n=0) Hyperglycemia criteria (n=7) Lack of efficacy (n=2) Lost to follow-up (n=57) Physician decision (n=3) Pregnancy(n=3) Protocol Violation (n=5) Study Terminated(n=1) Withdrawal by Subject (n=41) Metformin (n=624) Completed study (n=484)Completed study (n=482) Discontinued (n=142) Adverse experience (n=19) Creatinine/CrCl criteria (n=1) Hyperglycemia criteria (n=2) Lack of efficacy (n=12) Lost to follow-up (n=48) Physician decision (n=4) Pregnancy(n=2) Protocol Violation (n=14) Study Terminated(n=1) Withdrawal by Subject (n=39) CrCl=creatinine clearance; FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Baseline Patient Characteristics Sitagliptin/ metformin FDC (n=626) Metformin (n=624) Mean Age, y Sex, % Male Race, % White Asian Black Other Mean HbA 1c, % Mean FPG, mmol/L Mean weight, kg Mean BMI, kg/m Duration of diabetes, y BMI=body mass index; FDC=fixed-dose combination; FPG=fasting plasma glucose. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Study Design Day 1 Randomization Week 44 Screening period Phase A Phase B Screening 1 week 18 weeks a Metformin was initiated at 500 mg bid and titrated up to 1000 mg bid over 4 weeks. Patients who were unable to tolerate the maximum dose of sitagliptin/metformin FDC or metformin were allowed to be down-titrated to a minimum dose of sitagliptin/metformin FDC 50/500 mg bid or metformin 500 mg bid. bid=twice daily; FDC=fixed-dose combination; OHA=oral antihyperglycemic agent; qd=once daily; R=randomization; T2DM=type 2 diabetes mellitus. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5–9, Data on file, MSD. R 26 weeks Week 18 T2DM, aged 18–78 yrs, Off OHA ≥4 months, HbA 1c ≥7.5% Sitagliptin 50 mg bid + metformin 1000 bid a (n=626) Metformin 1000 mg bid a (n=624)

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: HbA 1c Results Over 18 Weeks HbA 1c LS Mean (±SE) Change From Baseline, % Week Sitagliptin/metformin FDC (n=560) Mean baseline HbA 1c =9.9% Metformin (n=566) Mean baseline HbA 1c =9.8% LS means difference – 0.6; P< FAS=full analysis set; FDC=fixed-dose combination; LS=least-squares; SE=standard error. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD. FAS Population

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: HbA 1c Results at 18 Weeks Sitagliptin/metformin FDC (n=560) Metformin (n=566) Mean baseline HbA 1c, % FAS Population a Between-groups difference. FAS=full analysis set; FDC=fixed-dose combination; LS=least-squares; SE=standard error. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD. –2.4 –1.8 –3 –2 –1 0 HbA 1C LS Mean (±SE) Change from Baseline, % –0.6 a ; P<0.001

FAS Population Mean Baseline HbA 1c, % a Between-groups difference. FAS=full analysis set; FDC=fixed-dose combination; LS=least-squares. Data on file, MSD. Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Subgroup Analysis of HbA 1c Results at 18 Weeks by Median Baseline HbA 1c Median Baseline HbA 1c ≤9.7% Median Baseline HbA 1c >9.7% –1.5 –3.3 –1.1 –2.4 –4 –3 –2 –1 0 HbA 1c LS Mean Change from Baseline, % –0.4 a ; P=0.003 –0.9 a ; P<0.001 n=288n=271n=291n=273 Sitagliptin/ metformin FDC (n=559) Metformin (n=564)

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Proportion of Patients at HbA 1c Goal of <7% at 18 Weeks FAS Population Patients at Goal, % Sitagliptin/metformin FDC (n=559) Metformin (n=564) P<0.001 a a Between-groups difference. FAS=full analysis set; FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD. Mean Baseline HbA 1c, %

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: FPG Results at 18 Weeks FAS Population –0.9 a ; P<0.001 FPG LS Mean (±SE) Change from Baseline, mmol/L FAS=full analysis set; FDC=fixed-dose combination; FPG=fasting plasma glucose; LS=least-squares; SE=standard error. a Between-groups difference. Data on file, MSD. –3.9 –3.0 –4.4 –3.3 –2.2 –1.1 0 Sitagliptin/ metformin FDC (n=560) Metformin (n=566) Mean baseline FPG, mmol/L 12.4 mmol/L 12.2 mmol/L

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Change from Baseline in HbA 1c by Baseline HbA 1c at Week 18 FAS=full analysis set; FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD. HbA 1c LS Mean Change from Baseline, % Baseline HbA 1c,% <8 ≥8 and <9 ≥9 and <10 ≥10 and <11 ≥11 FAS (Week 18) P=0.009 P<0.001 Mean HbA 1c, % n= –1.1 –1.6 –2.0 –2.9 –3.6 –2.7 –2.1 –1.7 –1.1 –0.8 –4.0 –3.5 –3.0 –2.5 –2.0 –1.5 –1.0 –0.5 0 Sitagliptin/metformin FDC Metformin P=0.158 P=0.111

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Markers of Beta-Cell Function at Week 18 Proinsulin-to- insulin ratio HOMA-β FAS Population n=458 n=469 n=456 n= a (P=0.004) –0.052 a (P=0.002) a Between-groups difference. FAS=full analysis set; FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD. Sitagliptin/metformin FDCMetformin LS Mean Change From Baseline Mean baseline value: Mean baseline value:

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Adverse Experience Summary at 18 Weeks APaT Population Clinical AEs a Sitagliptin/ metformin FDC (N=625) n (%) Metformin (N=621) n (%) With one or more AEs271 (43.4)301 (48.5) With no AEs354 (56.6)320 (51.5) With drug-related AEs b 109 (17.4)116 (18.7) With serious AEs13 (2.1)20 (3.2) With serious drug-related AEs b 1 (0.2) Who died1 (0.2) Discontinued due to AEs25 (4.0) Discontinued due to drug-related AEs b 18 (2.9)16 (2.6) Discontinued due to serious AEs6 (1.0)5 (0.8) Discontinued due to serious drug-related AEs b 1 (0.2) a Excluding data after initiation of an additional antihyperglycemic agent. b Considered by the investigator to be possibly, probably, or definitely drug-related. AE=adverse experience; APaT=all patients as treated; FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Prespecified Gastrointestinal AEs Over 18 Weeks Prespecificed Gastrointestinal AEs, % Sitagliptin/ metformin FDC n=625 Metformin n=621P value Diarrhea Nausea Vomiting Abdominal Pain b APaT Population a AE=adverse experience; APaT=all-patients-as-treated; FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD. a Excluding data after initiation of an additional antihyperglycemic agent. b Includes abdominal pain lower, abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric pain.

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Hypoglycemia Treatmentn/N (%) Episodes of Any Type Sitagliptin/metformin FDC13/625 (2.1) Metformin11/621 (1.8) Episodes Requiring Non-Medical Assistance and Not Exhibiting Marked Severity a Sitagliptin/metformin FDC0/625 (0.0) Metformin0/621 (0.0) Episodes Requiring Medical Assistance or Exhibiting Marked Severity a Sitagliptin/metformin FDC0/625 (0.0) Metformin0/621 (0.0) All Patients as Treated (Weeks 0–18) Excluding Data After Initiation of an Additional Antihyperglycemic Agent Data on file, MSD. a Marked severity includes markedly depressed level of consciousness, loss of consciousness, or seizure. FDC=fixed-dose combination.

JANUMET™ (sitagliptin/metformin, MSD) Indications: Based on the Worldwide Product Circular Indications – JANUMET is indicated in patients with type 2 diabetes mellitus to improve glycemic control As initial therapy when diet and exercise do not provide adequate glycemic control As an adjunct to diet and exercise in patients who have inadequate glycemic control on metformin or sitagliptin alone or in patients already being treated with the combination of sitagliptin and metformin In combination with a sulfonylurea (ie, triple combination therapy) as an adjunct to diet and exercise in patients who have inadequate glycemic control with any 2 of the 3 agents: metformin, sitagliptin, or a sulfonylurea In combination with a PPARγ agonist (ie, triple combination therapy) as an adjunct to diet and exercise in patients who have inadequate glycemic control with any 2 of the 3 agents: metformin, sitagliptin, or a PPARγ agonist (ie, thiazolidinediones) In combination with insulin as an adjunct to diet and exercise

Contraindications – JANUMET is contraindicated in patients with: Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females], or abnormal creatinine clearance, which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia. Known hypersensitivity to sitagliptin phosphate, metformin hydrochloride or any other component of JANUMET 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 the use of such products may result in acute alteration of renal function JANUMET™ (sitagliptin/metformin, MSD) Contraindications: Based on the Worldwide Product Circular

JANUMET™ (sitagliptin/metformin, MSD) Recommended Dosing: Based on Worldwide Product Circular  In general: twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side effects associated with metformin  Available dosage forms: – Sitagliptin 50 mg/metformin 500 mg; sitagliptin 50 mg/metformin 850 mg a ; sitagliptin 50 mg/metformin 1000 mg  Dosing recommendations: – As initial therapy for patients inadequately controlled with diet and exercise alone: Sitagliptin 50 mg/metformin 500 mg twice daily. May be titrated up to sitagliptin 50 mg/metformin 1000 mg – For patients inadequately controlled on metformin monotherapy: 50 mg twice daily (100 mg total daily dose) plus the current dose of metformin – For patients inadequately controlled on sitagliptin monotherapy: Sitagliptin 50 mg/metformin 500 mg twice daily. May titrate up to sitagliptin 50 mg/metformin 1000 mg – For patients switching from coadministration of sitagliptin and metformin: Initiate at current dose of sitagliptin and metformin a This dose should be considered for inclusion on a country-by-country basis.

 Dosing recommendations ( cont ) : – For patients inadequately controlled on dual combination therapy with any 2 of the following 3 antihyperglycemic agents: sitagliptin, metformin, or a sulfonylurea: 50 mg twice daily (100 mg total daily dose). Consider gradual dose escalation to reduce GI side effects associated with metformin. Patients may require lower sulfonylurea doses to reduce the risk of sulfonylurea-induced hypoglycemia – For patients inadequately controlled on dual combination therapy with any 2 of the following 3 antihyperglycemic agents: sitagliptin, metformin, and PPARγ agonist (ie thiazolidinediones): 50 mg twice daily (100 mg total daily dose). Consider gradual dose escalation to reduce GI side effects associated with metformin. – For patients inadequately controlled on dual combination therapy with any 2 of the following 3 antihyperglycemic agents: sitagliptin, metformin or insulin: 50 mg twice daily (100 mg total daily dose). Consider gradual dose escalation to reduce GI side effects associated with metformin. Patients currently on or initiating insulin therapy may require lower doses of insulin to reduce the risk of hypoglycemia.  Before initiation of therapy with JANUMET, and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and JANUMET discontinued if evidence of renal impairment is present. JANUMET™ (sitagliptin/metformin, MSD) Recommended Dosing ( cont ) : Based on Worldwide Product Circular

JANUMET™ (sitagliptin/metformin, MSD) Warnings and Precautions: Based on Worldwide Product Circular  In clinical studies, the most common adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea, upper respiratory tract infection, and headache (for initial sitagliptin and metformin combination therapy); nasopharyngitis (for sitagliptin monotherapy); and diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache (for metformin therapy).

Initial Fixed-Dose Combination Therapy With JANUMET™ vs Metformin Monotherapy: Conclusions Compared with metformin alone, in patients with type 2 diabetes and moderate to severe hyperglycemia on diet and exercise initial combination therapy with sitagliptin/metformin FDC (JANUMET) provided 1,2 Superior glycemic improvements resulting in more patients achieving HbA 1c goal A similar incidence of hypoglycemia, and lower incidences of abdominal pain and diarrhea compared with metformin alone. FDC=fixed-dose combination. 1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5 –9, Data on file, MSD.

Bibliography Data on file, MSD. Reasner C, Olnasky L, Seck TL, et al. Initial therapy with the fixed-dose combination (FDC) of sitagliptin and metformin (JANUMET™) in patients with type 2 diabetes mellitus provides superior glycemic control and hemoglobin A1C goal attainment with lower rates of abdominal pain and diarrhea versus metformin alone. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 5– 9, 2009.

Before prescribing JANUMET™ (sitagliptin/metformin, MSD), please read the Prescribing Information available at this presentation. Merck does not recommend the use of any product in any different manner than as described in the Prescribing Information. Copyright © 2009 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved JAN-09-PH-8029-SS (JAN-2009-W SS) Visit us on the World Wide Web at 26/F Philamlife Tower 8767 Paseo De Roxas, Makati City 1226 Tel No. (632) to 29 Fax No. (632) to 75