FDA label 7363101f-063b-416a-b90e-84c14b661148

5 WARNINGS AND PRECAUTIONS Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue STEGLATRO if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. ( 5.1 ) Lower Limb Amputation: Consider factors that may increase the risk of amputation before initiating STEGLATRO. Monitor patients for infections or ulcers of lower limbs, and discontinue if these occur. ( 5.2 ) Volume Depletion: May result in acute kidney injury. Before initiating, assess and correct volume status in patients with renal impairment or low systolic blood pressure, elderly patients, or patients on diuretics. Monitor for signs and symptoms during therapy. ( 5.3 ) Urosepsis and Pyelonephritis: Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated. ( 5.4 ) Hypoglycemia: Consider a lower dose of insulin or insulin secretagogue to reduce risk of hypoglycemia when used in combination. ( 5.5 ) Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): Serious, life-threatening cases have occurred in both females and males. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment. ( 5.6 ) Genital Mycotic Infections: Monitor and treat if indicated. ( 5.7 ) 5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, STEGLATRO significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose transporter 2 (SGLT2) inhibitors compared to patients who received placebo; this risk may be greater with higher doses. STEGLATRO is not indicated for glycemic control in patients with type 1 diabetes mellitus. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 4 days after discontinuing STEGLATRO [see Clinical Pharmacology (12.2) ]; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors. Consider ketone monitoring in patients at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue STEGLATRO, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting STEGLATRO. Withhold STEGLATRO, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume STEGLATRO when the patient is clinically stable and has resumed oral intake [see Dosage and Administration (2.3) ]. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue STEGLATRO and seek medical attention immediately if signs and symptoms occur. 5.2 Lower Limb Amputation In a long-term cardiovascular outcomes study [see Clinical Studies 14.2 ] , in patients with type 2 diabetes and established cardiovascular disease, the occurrence of non-traumatic lower limb amputations was reported with event rates of 4.7, 5.7, and 6.0 events per 1000 patient-years in the placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg treatment arms, respectively. Amputation of the toe and foot were most frequent (81 out of 109 patients with lower limb amputations). Some patients had multiple amputations, some involving both lower limbs. Lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation. Patients with amputations were more likely to be male, have higher A1C (%) at baseline, have a history of peripheral arterial disease, amputation or peripheral revascularization procedure, diabetic foot, and to have been taking diuretics or insulin. Across seven STEGLATRO clinical trials, non-traumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the STEGLATRO 5 mg group, and 8 (0.5%) patients in the STEGLATRO 15 mg group. Before initiating STEGLATRO, consider factors in the patient history that may predispose them to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy and diabetic foot ulcers. Counsel patients about the importance of routine preventative foot care. Monitor patients receiving STEGLATRO for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue STEGLATRO if these complications occur. 5.3 Volume Depletion STEGLATRO can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine [see Adverse Reactions (6.1) ] . There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including STEGLATRO. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m 2 ) [see Use in Specific Populations (8.6) ] , elderly patients, patients with low systolic blood pressure, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating STEGLATRO in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating STEGLATRO. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy. 5.4 Urosepsis and Pyelonephritis There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated [see Adverse Reactions (6.1) ] . 5.5 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. STEGLATRO may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue [see Adverse Reactions (6.1) ] . Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with STEGLATRO. 5.6 Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) Reports of necrotizing fasciitis of the perineum (Fournier's Gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including STEGLATRO. Cases have been reported in females and males. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with STEGLATRO presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue STEGLATRO, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control. 5.7 Genital Mycotic Infections STEGLATRO increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections [see Adverse Reactions (6.1) ] . Monitor and treat appropriately.

6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes and Other Ketoacidosis [see Warnings and Precautions (5.1) ] Lower Limb Amputation [see Warnings and Precautions (5.2) ] Volume Depletion [see Warnings and Precautions (5.3) ] Urosepsis and Pyelonephritis [see Warnings and Precautions (5.4) ] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.5) ] Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) [see Warnings and Precautions (5.6) ] Genital Mycotic Infections [see Warnings and Precautions (5.7) ] Most common adverse reactions (incidence ≥ 5%) were female genital mycotic infections. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Pool of Placebo-Controlled Trials Evaluating STEGLATRO 5 and 15 mg The data in Table 1 are derived from a pool of three 26-week, placebo-controlled trials. STEGLATRO was used as monotherapy in one trial and as add-on therapy in two trials [see Clinical Studies (14) ] . These data reflect exposure of 1,029 patients to STEGLATRO with a mean exposure duration of approximately 25 weeks. Patients received STEGLATRO 5 mg (N=519), STEGLATRO 15 mg (N=510), or placebo (N=515) once daily. The mean age of the population was 57 years and 2% were older than 75 years of age. Fifty-three percent (53%) of the population was male and 73% were Caucasian, 15% were Asian, and 7% were Black or African American. At baseline the population had diabetes for an average of 7.5 years, had a mean HbA1c of 8.1%, and 19.4% had established microvascular complications of diabetes. Baseline renal function (mean eGFR 88.9 mL/min/1.73 m 2 ) was normal or mildly impaired in 97% of patients and moderately impaired in 3% of patients. Table 1 shows common adverse reactions associated with the use of STEGLATRO. These adverse reactions were not present at baseline, occurred more commonly on STEGLATRO than on placebo, and occurred in at least 2% of patients treated with either STEGLATRO 5 mg or STEGLATRO 15 mg. Table 1: Adverse Reactions Reported in ≥2% of Patients with Type 2 Diabetes Mellitus Treated with STEGLATRO The three placebo-controlled studies included one monotherapy trial and two add-on combination trials with metformin or with metformin and sitagliptin. and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of STEGLATRO Monotherapy or Combination Therapy Number (%) of Patients Placebo N = 515 STEGLATRO 5 mg N = 519 STEGLATRO 15 mg N = 510 Female genital mycotic infections Includes: genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis. Percentages calculated with the number of female patients in each group as denominator: placebo (N=235), STEGLATRO 5 mg (N=252), STEGLATRO 15 mg (N=245). 3.0% 9.1% 12.2% Male genital mycotic infections Includes: balanitis candida, balanoposthitis, genital infection, and genital infection fungal. Percentages calculated with the number of male patients in each group as denominator: placebo (N=280), STEGLATRO 5 mg (N=267), STEGLATRO 15 mg (N=265). 0.4% 3.7% 4.2% Urinary tract infections Includes: cystitis, dysuria, streptococcal urinary tract infection, urethritis, urinary tract infection. 3.9% 4.0% 4.1% Headache 2.3% 3.5% 2.9% Vaginal pruritus Includes: vulvovaginal pruritus and pruritus genital. Percentages calculated with the number of female patients in each group as denominator: placebo (N=235), ertugliflozin 5 mg (N=252), ertugliflozin 15 mg (N=245). 0.4% 2.8% 2.4% Increased urination Includes: pollakiuria, micturition urgency, polyuria, urine output increased, and nocturia. 1.0% 2.7% 2.4% Nasopharyngitis 2.3% 2.5% 2.0% Back pain 2.3% 1.7% 2.5% Weight decreased 1.0% 1.2% 2.4% Thirst Includes: thirst, dry mouth, polydipsia, and dry throat. 0.6% 2.7% 1.4% Volume Depletion STEGLATRO causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion, particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m 2 ). In patients with moderate renal impairment, adverse reactions related to volume depletion (e.g., dehydration, dizziness postural, presyncope, syncope, hypotension, and orthostatic hypotension) were reported in 0%, 4.4%, and 1.9% of patients treated with placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively. STEGLATRO may also increase the risk of hypotension in other patients at risk for volume contraction [see Use in Specific Populations (8.5 , 8.6) ] . Hypoglycemia The incidence of hypoglycemia by study is shown in Table 2 . Table 2: Incidence of Overall Overall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL. and Severe Severe hypoglycemic events: required assistance, lost consciousness, or experienced a seizure regardless of blood glucose. Hypoglycemia in Placebo-Controlled Clinical Studies in Patients with Type 2 Diabetes Mellitus Monotherapy (26 weeks) Placebo (N = 153) STEGLATRO 5 mg (N =156) STEGLATRO 15 mg (N = 152) Overall [N (%)] 1 (0.7) 4 (2.6) 4 (2.6) Severe [N (%)] 0 (0.0) 0 (0.0) 2 (1.3) Add-on Combination Therapy with Metformin (26 weeks) Placebo (N = 209) STEGLATRO 5 mg (N = 207) STEGLATRO 15 mg (N = 205) Overall [N (%)] 9 (4.3) 15 (7.2) 16 (7.8) Severe [N (%)] 1 (0.5) 1 (0.5) 0 (0.0) Add-on Combination Therapy with Metformin and Sitagliptin (26 weeks) Placebo (N = 153) STEGLATRO 5 mg (N = 156) STEGLATRO 15 mg (N = 153) Overall [N (%)] 5 (3.3) 7 (4.5) 3 (2.0) Severe [N (%)] 1 (0.7) 1 (0.6) 0 (0.0) In Combination with Insulin and/or an Insulin Secretagogue in Patients with Moderate Renal Impairment (26 weeks) Placebo (N = 133) STEGLATRO 5 mg (N = 148) STEGLATRO 15 mg (N = 143) Overall [N (%)] 48 (36.1) 53 (35.8) 39 (27.3) Severe [N (%)] 3 (2.3) 5 (3.4) 3 (2.1) Add-on Combination with Insulin with or without Metformin (18 weeks) Placebo (N = 347) STEGLATRO 5 mg (N = 348) STEGLATRO 15 mg (N = 370) Overall [N (%)] 130 (37.5) 137 (39.4) 144 (38.9) Severe [N (%)] 12 (3.5) 13 (3.7) 19 (5.1) Add-on Combination with a Sulfonylurea (18 weeks) Placebo (N =48) STEGLATRO 5 mg (N =55) STEGLATRO 15 mg (N =54) Overall [N (%)] 2 (4.2) 4 (7.3) 5 (9.3) Severe [N (%)] 0 (0.0) 0 (0.0) 0 (0.0) Add-on Combination with Metformin and a Sulfonylurea (18 weeks) Placebo (N = 117) STEGLATRO 5 mg (N = 100) STEGLATRO 15 mg (N = 113) Overall [N (%)] 17 (14.5) 20 (20.0) 30 (26.5) Severe [N (%)] 1 (0.9) 2 (2.0) 2 (1.8) Genital Mycotic Infections In the pool of three placebo-controlled clinical trials, the incidence of female genital mycotic infections (e.g., genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginitis) occurred in 3%, 9.1%, and 12.2% of females treated with placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively (see Table 1 ). In females, discontinuation due to genital mycotic infections occurred in 0% and 0.6% of patients treated with placebo and STEGLATRO, respectively. In the same pool, male genital mycotic infections (e.g., balanitis candida, balanoposthitis, genital infection, genital infection fungal) occurred in 0.4%, 3.7%, and 4.2% of males treated with placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively (see Table 1 ). Male genital mycotic infections occurred more commonly in uncircumcised males. In males, discontinuations due to genital mycotic infections occurred in 0% and 0.2% of patients treated with placebo and STEGLATRO, respectively. Phimosis was reported in 8 of 1729 (0.5%) male ertugliflozin-treated patients, of which four required circumcision. Urinary Tract Infections In VERTIS CV, urinary tract infections (e.g., urinary tract infection, cystitis, dysuria) occurred in 10.2%, 12.2% and 12.0% of patients treated with placebo, STEGLATRO 5 mg and STEGLATRO 15 mg, respectively. The incidences of serious urinary tract infections were 0.8%, 0.9% and 0.4% with placebo, STEGLATRO 5 mg and STEGLATRO 15 mg, respectively. Laboratory Tests Changes in Serum Creatinine and eGFR Initiation of STEGLATRO causes an increase in serum creatinine and decrease in eGFR within weeks of starting therapy and then these changes stabilize. In a study of patients with moderate renal impairment, larger mean changes were observed. In a long-term cardiovascular outcomes trial, an initial increase in serum creatinine and a decrease in eGFR within weeks of starting therapy was observed (at Week 6 eGFR changes of -2.7, -3.8 and -0.4 mL/min/1.73 m 2 in the STEGLATRO 5 mg, STEGLATRO 15 mg and placebo arms, respectively). The initial decline was followed by a recovery toward baseline to Week 52 (eGFR change from baseline of - 0.4, - 1.1 and - 0.2 mL/min/1.73 m 2 in STEGLATRO 5 mg, STEGLATRO 15 mg, and placebo arms, respectively). Acute hemodynamic changes may play a role in the early renal function changes observed with STEGLATRO since they are reversed after treatment discontinuation. Increases in Low-Density Lipoprotein Cholesterol (LDL-C) In the pool of three placebo-controlled trials, dose-related increases in LDL-C were observed in patients treated with STEGLATRO. Mean percent changes from baseline to Week 26 in LDL-C relative to placebo were 2.6% and 5.4% with STEGLATRO 5 mg and STEGLATRO 15 mg, respectively. The range of mean baseline LDL-C was 96.6 to 97.7 mg/dL across treatment groups. Increases in Hemoglobin In the pool of three placebo-controlled trials, mean changes (percent changes) from baseline to Week 26 in hemoglobin were -0.21 g/dL (-1.4%) with placebo, 0.46 g/dL (3.5%) with STEGLATRO 5 mg, and 0.48 g/dL (3.5%) with STEGLATRO 15 mg. The range of mean baseline hemoglobin was 13.90 to 14.00 g/dL across treatment groups. At the end of treatment, 0.0%, 0.2%, and 0.4% of patients treated with placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively, had a hemoglobin increase greater than 2 g/dL and above the upper limit of normal. Increases in Serum Phosphate In the pool of three placebo-controlled trials, mean changes (percent changes) from baseline in serum phosphate were 0.04 mg/dL (1.9%) with placebo, 0.21 mg/dL (6.8%) with STEGLATRO 5 mg, and 0.26 mg/dL (8.5%) with STEGLATRO 15 mg. The range of mean baseline serum phosphate was 3.53 to 3.54 mg/dL across treatment groups. In a clinical trial of patients with moderate renal impairment, mean changes (percent changes) from baseline at Week 26 in serum phosphate were -0.01 mg/dL (0.8%) with placebo, 0.29 mg/dL (9.7%) with STEGLATRO 5 mg, and 0.24 mg/dL (7.8%) with STEGLATRO 15 mg. 6.2 Postmarketing Experience Additional adverse reactions have been identified during postapproval use. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Necrotizing fasciitis of the perineum (Fournier's Gangrene) Angioedema Rash

<table width="90%"><caption>Table 1: Adverse Reactions Reported in &#x2265;2% of Patients with Type 2 Diabetes Mellitus Treated with STEGLATRO<footnote ID="foot11">The three placebo-controlled studies included one monotherapy trial and two add-on combination trials with metformin or with metformin and sitagliptin.</footnote> and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of STEGLATRO Monotherapy or Combination Therapy</caption><col width="40%" align="left" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule Botrule" colspan="3">Number (%) of Patients</th></tr><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">Placebo N = 515</th><th styleCode="Rrule">STEGLATRO 5 mg N = 519</th><th styleCode="Rrule">STEGLATRO 15 mg N = 510</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Female genital mycotic infections<footnote ID="foot12">Includes: genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis. Percentages calculated with the number of female patients in each group as denominator: placebo (N=235), STEGLATRO 5 mg (N=252), STEGLATRO 15 mg (N=245).</footnote></td><td styleCode="Rrule">3.0%</td><td styleCode="Rrule">9.1%</td><td styleCode="Rrule">12.2%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Male genital mycotic infections<footnote ID="foot13">Includes: balanitis candida, balanoposthitis, genital infection, and genital infection fungal. Percentages calculated with the number of male patients in each group as denominator: placebo (N=280), STEGLATRO 5 mg (N=267), STEGLATRO 15 mg (N=265).</footnote></td><td styleCode="Rrule">0.4%</td><td styleCode="Rrule">3.7%</td><td styleCode="Rrule">4.2%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Urinary tract infections<footnote styleCode="foot14">Includes: cystitis, dysuria, streptococcal urinary tract infection, urethritis, urinary tract infection. </footnote></td><td styleCode="Rrule">3.9%</td><td styleCode="Rrule">4.0%</td><td styleCode="Rrule">4.1%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">2.3%</td><td styleCode="Rrule">3.5%</td><td styleCode="Rrule">2.9%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Vaginal pruritus<footnote ID="foot15">Includes: vulvovaginal pruritus and pruritus genital. Percentages calculated with the number of female patients in each group as denominator: placebo (N=235), ertugliflozin 5 mg (N=252), ertugliflozin 15 mg (N=245).</footnote></td><td styleCode="Rrule">0.4%</td><td styleCode="Rrule">2.8%</td><td styleCode="Rrule">2.4%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased urination<footnote ID="foot16">Includes: pollakiuria, micturition urgency, polyuria, urine output increased, and nocturia.</footnote></td><td styleCode="Rrule">1.0%</td><td styleCode="Rrule">2.7%</td><td styleCode="Rrule">2.4%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nasopharyngitis</td><td styleCode="Rrule">2.3%</td><td styleCode="Rrule">2.5%</td><td styleCode="Rrule">2.0%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Back pain</td><td styleCode="Rrule">2.3%</td><td styleCode="Rrule">1.7%</td><td styleCode="Rrule">2.5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Weight decreased</td><td styleCode="Rrule">1.0%</td><td styleCode="Rrule">1.2%</td><td styleCode="Rrule">2.4%</td></tr><tr><td styleCode="Lrule Rrule">Thirst<footnote ID="foot17">Includes: thirst, dry mouth, polydipsia, and dry throat.</footnote></td><td styleCode="Rrule">0.6%</td><td styleCode="Rrule">2.7%</td><td styleCode="Rrule">1.4%</td></tr></tbody></table>

<table width="90%"><caption>Table 2: Incidence of Overall<footnote ID="foot31">Overall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL.</footnote> and Severe<footnote ID="foot32">Severe hypoglycemic events: required assistance, lost consciousness, or experienced a seizure regardless of blood glucose.</footnote> Hypoglycemia in Placebo-Controlled Clinical Studies in Patients with Type 2 Diabetes Mellitus</caption><col width="40%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Monotherapy (26 weeks)</content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N = 153)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N =156)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N = 152)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)] </td><td styleCode="Rrule">1 (0.7)</td><td styleCode="Rrule">4 (2.6)</td><td styleCode="Rrule">4 (2.6)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Severe [N (%)] </td><td styleCode="Rrule">0 (0.0)</td><td styleCode="Rrule">0 (0.0)</td><td styleCode="Rrule">2 (1.3)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Add-on Combination Therapy with Metformin (26 weeks)</content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N = 209)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N = 207)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N = 205)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)] </td><td styleCode="Rrule">9 (4.3)</td><td styleCode="Rrule">15 (7.2)</td><td styleCode="Rrule">16 (7.8)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Severe [N (%)] </td><td styleCode="Rrule">1 (0.5)</td><td styleCode="Rrule">1 (0.5)</td><td styleCode="Rrule">0 (0.0)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Add-on Combination Therapy with Metformin and Sitagliptin (26 weeks) </content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N = 153)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N = 156)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N = 153)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)] </td><td styleCode="Rrule">5 (3.3)</td><td styleCode="Rrule">7 (4.5)</td><td styleCode="Rrule">3 (2.0)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Severe [N (%)] </td><td styleCode="Rrule">1 (0.7)</td><td styleCode="Rrule">1 (0.6)</td><td styleCode="Rrule">0 (0.0)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">In Combination with Insulin and/or an Insulin Secretagogue in Patients with Moderate Renal Impairment (26 weeks)</content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N = 133)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N = 148)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N = 143)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)]</td><td styleCode="Rrule">48 (36.1)</td><td styleCode="Rrule">53 (35.8)</td><td styleCode="Rrule">39 (27.3)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Severe [N (%)]</td><td styleCode="Rrule">3 (2.3)</td><td styleCode="Rrule">5 (3.4)</td><td styleCode="Rrule">3 (2.1)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Add-on Combination with Insulin with or without Metformin (18 weeks)</content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N = 347)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N = 348)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N = 370)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)]</td><td styleCode="Rrule">130 (37.5)</td><td styleCode="Rrule">137 (39.4)</td><td styleCode="Rrule">144 (38.9)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Severe [N (%)]</td><td styleCode="Rrule">12 (3.5)</td><td styleCode="Rrule">13 (3.7)</td><td styleCode="Rrule">19 (5.1)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Add-on Combination with a Sulfonylurea (18 weeks)</content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N =48)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N =55)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N =54)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)]</td><td styleCode="Rrule">2 (4.2)</td><td styleCode="Rrule">4 (7.3)</td><td styleCode="Rrule">5 (9.3)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Severe [N (%)]</td><td styleCode="Rrule">0 (0.0)</td><td styleCode="Rrule">0 (0.0)</td><td styleCode="Rrule">0 (0.0)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Add-on Combination with Metformin and a Sulfonylurea (18 weeks)</content></td><td styleCode="Rrule"><content styleCode="bold">Placebo (N = 117)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 5 mg (N = 100)</content></td><td styleCode="Rrule"><content styleCode="bold">STEGLATRO 15 mg (N = 113)</content></td></tr><tr><td styleCode="Lrule Rrule">Overall [N (%)]</td><td styleCode="Rrule">17 (14.5)</td><td styleCode="Rrule">20 (20.0)</td><td styleCode="Rrule">30 (26.5)</td></tr><tr><td styleCode="Lrule Rrule">Severe [N (%)]</td><td styleCode="Rrule">1 (0.9)</td><td styleCode="Rrule">2 (2.0)</td><td styleCode="Rrule">2 (1.8)</td></tr></tbody></table>