Forxiga film-coated tablets 10 mg blister No. 30

Instructions Forxiga film-coated tablets 10 mg blister No. 30

Composition

active ingredient: dapagliflozin;

1 film-coated tablet contains 6.15 mg or 12.30 mg of dapagliflozin propanediol monohydrate equivalent to dapagliflozin 5 mg or 10 mg;

excipients: microcrystalline cellulose, anhydrous lactose, crospovidone, silicon dioxide, magnesium stearate, Opadry II yellow.

Dosage form

Film-coated tablets.

Main physicochemical properties:

5 mg tablets: yellow, round, biconvex, film-coated tablets, engraved with 5 on one side and 1427 on the other side;

10 mg tablets: yellow, biconvex, diamond-shaped tablets, film-coated, engraved with 10 on one side and 1428 on the other side.

Pharmacotherapeutic group

Drugs used in diabetes mellitus, inhibitors of sodium-dependent glucose cotransporter type 2 (NSCG2i). ATC code A10VK01.

Pharmacological properties

Pharmacodynamics

Mechanism of action

Dapagliflozin is a highly potent (Ki: 0.55 nM), selective and reversible inhibitor of sodium-dependent glucose cotransporter type 2 (SDG2i).

Inhibition of iNGCT2 by dapagliflozin reduces glucose reabsorption from the glomerular filtrate in the proximal renal tubule with a concomitant decrease in sodium reabsorption, leading to urinary glucose excretion and osmotic diuresis. Thus, dapagliflozin increases sodium delivery to the distal tubule, which increases tubuloglomerular feedback and reduces intraglomerular pressure. This, in combination with osmotic diuresis, contributes to the reduction of volume overload, blood pressure, and preload and afterload, which may have a positive effect on cardiac remodeling and the preservation of renal function. Other effects include increased hematocrit and weight loss. The cardiac and renal benefits of dapagliflozin are not solely dependent on the blood glucose-lowering effect and are not limited to patients with diabetes, as demonstrated in the DAPA-HF and DAPA-CKD studies.

Dapagliflozin improves fasting and postprandial plasma glucose levels by reducing renal glucose reabsorption, resulting in urinary glucose excretion. This glucose excretion (glucuretic effect) is observed after the first dose of the drug, persists over the 24-hour dosing interval, and is maintained throughout treatment. The amount of glucose excreted by the kidneys by this mechanism depends on the blood glucose concentration and glomerular filtration rate (GFR). Therefore, in patients with normal blood glucose levels, dapagliflozin has a low potential to cause hypoglycemia. Dapagliflozin does not disrupt normal endogenous glucose production in response to hypoglycemia. Dapagliflozin acts independently of insulin secretion and action. In clinical studies with dapagliflozin, improvements in beta-cell function (beta-cell NOMA) were observed in the homeostasis model assessment.

NGKTG2 is selectively expressed in the kidney. Dapagliflozin does not inhibit other glucose transporters, which are important for glucose transport into peripheral tissues, and is >1400-fold more selective for NGKTG2 compared to NGKTG1, the major transporter in the intestine responsible for glucose absorption.

Pharmacodynamic effects

In healthy subjects and patients with type 2 diabetes, an increase in the amount of glucose excreted in the urine was observed after the use of dapagliflozin. Approximately 70 g of glucose per day (corresponding to 280 kcal/day) was excreted in the urine when dapagliflozin was administered at a dose of 10 mg/day to patients with type 2 diabetes for 12 weeks. In patients with type 2 diabetes who received dapagliflozin at a dose of 10 mg/day for a period of up to 2 years, signs of prolonged glucose excretion were observed.

This urinary glucose excretion with dapagliflozin also results in osmotic diuresis and increased urine volume in patients with type 2 diabetes. The increase in urine volume in patients with type 2 diabetes is approximately 375 mL/day. The increase in urine volume was associated with a small and transient increase in urinary sodium excretion, which was not accompanied by changes in serum sodium concentration.

Urinary uric acid excretion was also transiently increased (for 3–7 days) and was accompanied by a sustained decrease in serum uric acid concentration. At 24 weeks, the decrease in serum uric acid concentration ranged from –48.3 to –18.3 μmol/L (–0.87 to –0.33 mg/dL).

Clinical efficacy and safety

Type 2 diabetes

Fourteen double-blind, randomized, controlled clinical trials were conducted in 7,056 adult patients with type 2 diabetes mellitus to evaluate the glycemic efficacy and safety of Forxiga; 4,737 patients in these trials received dapagliflozin. Twelve trials had a treatment duration of 24 weeks, 8 had long-term extensions ranging from 24 to 80 weeks (for a total study duration of 104 weeks), one trial had a treatment duration of 28 weeks, and one trial had a treatment duration of 52 weeks with long-term extensions of 52 and 104 weeks (for a total study duration of 208 weeks). The median duration of diabetes in the participants ranged from 1.4 to 16.9 years. 50% had mild renal impairment and 11% had moderate renal impairment. 51% of participants were male, 84% were Caucasian, 8% were Asian, 4% were Black, and 4% were other races. 81% of participants had a body mass index (BMI) ≥ 27. In addition, two 12-week placebo-controlled studies were conducted in patients with inadequately controlled type 2 diabetes mellitus and hypertension.

A clinical trial evaluating cardiovascular events (DECLARE) was conducted with dapagliflozin 10 mg compared with placebo in 17,160 patients with type 2 diabetes with or without established cardiovascular disease to evaluate the effect on cardiovascular and renal events.

Glycemic control

Monotherapy

A 24-week, double-blind, placebo-controlled study (with an additional extension period) was conducted to evaluate the safety and efficacy of Forxiga monotherapy in patients with inadequately controlled type 2 diabetes. Dapagliflozin once daily resulted in statistically significant (p < 0.0001) reductions in glycosylated hemoglobin (HbA1c) compared to placebo (Table 1).

In the extension period, the reduction in HbA1c was maintained up to and including week 102 (adjusted mean change from baseline of -0.61% and -0.17% for dapagliflozin 10 mg and placebo, respectively).

Table 1. Results after 24 weeks (PVDOSA) of a placebo-controlled study of dapagliflozin as monotherapy

and PVDOS – carry forward of the data of the last observation (before treatment of treated patients).

b All randomized patients who received at least one dose of study drug in the short-term double-blind period of the study.

c Least squares mean adjusted to the original value.

* p-value < 0.0001 compared to placebo.

Statistical significance was not assessed as a result of the sequential testing procedure for secondary endpoints.

Additional combination therapy

In a 52-week, active-controlled, non-inferiority study (with 52-week and 104-week extension periods), Forxiga was evaluated as add-on to metformin compared to a sulfonylurea (glipizide) as add-on to metformin in patients with inadequate glycemic control (HbA1c ˃ 6.5% and ≤ 10%). Results showed similar mean reductions from baseline in HbA1c at 52 weeks compared to glipizide, demonstrating non-inferiority of the study drug. At 104 weeks, the adjusted mean change from baseline in HbA1c was -0.32% for dapagliflozin and -0.14% for glipizide. At 208 weeks, the adjusted mean change from baseline in HbA1c was -0.10% for dapagliflozin and 0.20% for glipizide. At 52, 104, and 208 weeks, significantly fewer patients in the dapagliflozin group (3.5%, 4.3%, and 5.0%, respectively) experienced at least one episode of hypoglycemia compared with the glipizide group (40.8%, 47.0%, and 50.0%, respectively). The proportion of patients who remained in the study at 104 and 208 weeks was 56.2% and 39.7% for the dapagliflozin group and 50.0% and 34.6% for the glipizide group.

The reduction in HbA1c observed at 24 weeks was maintained in the add-on combination therapy studies (glimepiride and insulin) up to 48 weeks (glimepiride) and up to 104 weeks (insulin). After 48 weeks, when added to sitagliptin (with or without metformin), the adjusted mean change from baseline for dapagliflozin 10 mg and placebo was -0.30% and 0.38%, respectively. In the add-on study with metformin, the reduction in HbA1c was maintained at 102 weeks (adjusted mean change from baseline -0.78% and 0.02% for dapagliflozin 10 mg and placebo, respectively). After 104 weeks of insulin use (with or without additional oral hypoglycemic agents), the adjusted mean change from baseline in HbA1c reduction was -0.71% and -0.06% for dapagliflozin 10 mg and placebo, respectively. After 48 and 104 weeks, insulin dose remained stable from baseline in patients receiving dapagliflozin 10 mg, averaging 76 IU/day. In the placebo group, the mean dose increases were 10.5 IU/day and 18.3 IU/day from baseline (mean dose 84 and 92 IU/day) at 48 and 104 weeks, respectively. The proportion of patients who continued to participate in the study after 104 weeks was 72.4% in the dapagliflozin 10 mg treatment group and 54.8% in the placebo group.

Use in combination with metformin in previously untreated patients

A total of 1236 previously untreated patients with inadequately controlled type 2 diabetes (HbAlc ≥ 7.5% and ≤ 12%) participated in two 24-week active-controlled studies to evaluate the efficacy and safety of dapagliflozin (5 mg or 10 mg) in combination with metformin in previously untreated patients compared with monotherapy.

Treatment with dapagliflozin 10 mg in combination with metformin (up to 2000 mg daily) provided significant improvements in HbA1c compared to treatment with single monocomponent drugs (Table 2) and resulted in greater reductions in fasting plasma glucose (FPG) (compared to treatment with single monocomponent drugs) and body weight (compared to metformin).

Table 2: Results at Week 24 (PVDOSA) in an active-controlled study of combination therapy with dapagliflozin and metformin in previously untreated patients

aPVDOS – carry forward the data of the last observation.

b All randomized patients who received at least one dose of double-blind study drug during the short-term double-blind period.

c Least squares mean adjusted for the original value.

* p-value < 0.0001.

Combination therapy with prolonged-release exenatide

In a 28-week, double-blind, active-controlled study, the combination of dapagliflozin and prolonged-release exenatide (a GLP-1 receptor agonist) was compared with dapagliflozin alone and prolonged-release exenatide alone in patients with inadequately controlled diabetes on metformin monotherapy (HbA1c ≥ 8% and ≤ 12%). All treatment groups showed a reduction in HbA1c from baseline. The combination of dapagliflozin 10 mg and prolonged-release exenatide resulted in a significant reduction in HbA1c from baseline compared with dapagliflozin and prolonged-release exenatide alone (Table 3).

Table 3. Results of one 28-week study of dapagliflozin and extended-release exenatide compared to treatment with dapagliflozin alone and extended-release exenatide alone in combination with metformin (pool of all patients randomized according to assigned treatment)

1 r/d = once daily. 1 r/w = once weekly. N = number of patients. CI = confidence interval

a The least squares mean adjusted for baseline and the difference between treatment groups in change from baseline at week 28 are modeled using a mixed model with repeated measures including treatment, region, baseline HbA1c (< 9.0% or ≥ 9.0%), week, and weekly treatment as fixed factors and baseline as a covariate.

*p<0.001.

**p<0.01.

p-values – all adjusted p-values for multiplicity.

Analyses exclude measurements after rescue therapy and after early discontinuation of study drug.

Fasting plasma glucose levels

Dapagliflozin 10 mg, as monotherapy or as add-on to metformin, glimepiride, metformin and a sulfonylurea, sitagliptin (with or without metformin), or insulin, resulted in statistically significant reductions in ALP (-1.90 to -1.20 mmol/L [-34.2 to -21.7 mg/dL]) compared to placebo (-0.33 to 0.21 mmol/L [-6.0 to 3.8 mg/dL]). This effect was observed at week 1 of treatment and was maintained in studies extended to week 104.

Combination therapy with dapagliflozin 10 mg and extended-release exenatide resulted in a significantly greater reduction in ALP at week 28: –3.66 mmol/L (–65.8 mg/dL), compared with –2.73 mmol/L (–49.2 mg/dL) with dapagliflozin alone (p < 0.001) and –2.54 mmol/L (–45.8 mg/dL) with exenatide alone (p < 0.001).

In a dedicated study in patients with diabetes mellitus with eGFR ≥ 45 to < 60 mL/min/1.73 m2, treatment with dapagliflozin demonstrated a reduction in GFR at 24 weeks: -1.19 mmol/L (-21.46 mg/dL) compared with -0.27 mmol/L (-4.87 mg/dL) for placebo (p = 0.001).

Plasma glucose levels after meals

Treatment with dapagliflozin 10 mg in addition to glimepiride treatment resulted in statistically significant reductions in 2-hour postprandial plasma glucose levels at 24 weeks, with these values maintained through week 48.

Treatment with dapagliflozin 10 mg as an add-on to sitagliptin (with or without metformin) resulted in a reduction in 2-hour postprandial glucose levels at week 24 that was maintained through week 48.

Combination therapy with dapagliflozin 10 mg and extended-release exenatide resulted in significant reductions in 2-hour postprandial glucose levels at 28 weeks compared with single agents.

Body weight

Dapagliflozin 10 mg as add-on to metformin, glimepiride, metformin and a sulfonylurea, sitagliptin (with or without metformin), or insulin resulted in statistically significant weight reductions at 24 weeks (p < 0.0001). These effects were maintained in long-term studies. At 48 weeks, the difference from placebo for dapagliflozin as add-on to sitagliptin (with or without metformin) was -2.22 kg. At 102 weeks, the difference from placebo for dapagliflozin as add-on to metformin or insulin was -2.14 and -2.88 kg, respectively.

In an active-controlled non-inferiority trial, dapagliflozin as an add-on to metformin resulted in a statistically significant weight loss compared to glipizide: –4.65 kg at 52 weeks (p < 0.0001), which was maintained at 104 and 208 weeks (–5.06 kg and –4.38 kg, respectively).

The combination of dapagliflozin 10 mg and extended-release exenatide demonstrated greater weight loss compared to therapy with either drug alone (Table 3).

Results from a 24-week study in 182 patients with diabetes using dual-energy X-ray absorptiometry to assess body composition showed greater reductions in body weight and fat mass, rather than in lean body mass or fluid loss, in patients treated with dapagliflozin 10 mg and metformin compared to placebo and metformin. Treatment with Forxiga and metformin resulted in numerical reductions in visceral fat compared to placebo and metformin, as measured by a substudy using magnetic resonance imaging.

Blood pressure

In a pre-planned pooled analysis of 13 placebo-controlled trials, treatment with dapagliflozin 10 mg resulted in a change from baseline in systolic blood pressure of -3.7 mmHg and diastolic blood pressure of -1.8 mmHg compared with -0.5 mmHg for systolic and -0.5 mmHg for diastolic blood pressure in the placebo group at week 24. Similar reductions were observed throughout the study period up to 104 weeks.

In two 12-week placebo-controlled studies, a total of 1062 patients with inadequately controlled type 2 diabetes mellitus and hypertension (despite ongoing treatment with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in one study and ACEI or ARB plus one antihypertensive medicinal product in the other study) were treated with dapagliflozin 10 mg or placebo. By week 12, in both studies, dapagliflozin 10 mg in combination with usual antidiabetic treatment provided improvements in HbA1c and placebo-adjusted reductions in systolic blood pressure by a mean of 3.1 and 4.3 mmHg, respectively.

In a dedicated study in diabetic patients with eGFR ≥45 to <60 mL/min/1.73 m2, dapagliflozin treatment demonstrated a reduction in systolic blood pressure at 24 weeks: -4.8 mmHg compared to placebo -1.7 mmHg (p<0.05).

Glycaemic control in patients with moderate renal impairment (chronic kidney disease 3A CKD) (estimated glomerular filtration rate (eGFR) ≥ 45 to < 60 mL/min/1.73m2)

The efficacy of dapagliflozin was also evaluated separately in a dedicated study in patients with diabetes mellitus with eGFR ≥ 45 mL/min/1.73 m2 to < 60 mL/min/1.73 m2 who had inadequate glycaemic control on conventional therapy. Treatment with dapagliflozin resulted in reductions in HbA1c and body weight compared with placebo (Table 4).

Table 4. Results of a placebo-controlled study of dapagliflozin in patients with diabetes mellitus with eGFR ≥45 to <60 mL/min/1.73m2 at 24 weeks

a Metformin or metformin hydrochloride was part of usual care in 69.4% and 64.0% of patients for the dapagliflozin and placebo groups, respectively.

b Least squares mean adjusted for the original value.

c Derivatives of the least squares mean, adjusted for the original value.

* p<0.001

Patients with baseline HbA1c ≥ 9%

In a pre-planned analysis in patients with baseline HbA1c ≥ 9.0%, dapagliflozin 10 mg monotherapy (adjusted mean change from baseline: -2.04% and 0.19% for dapagliflozin 10 mg and placebo, respectively) and dapagliflozin add-on to metformin (adjusted mean change from baseline: -1.32% and -0.53% for dapagliflozin and placebo, respectively) resulted in statistically significant reductions in HbA1c levels at week 24.

Cardiovascular and renal outcomes

The Effect of Dapagliflozin on Cardiovascular Events (DECLARE) trial was an international, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to determine the effect of dapagliflozin compared to placebo on cardiovascular outcomes when added to current background therapy. All patients had type 2 diabetes and at least two additional cardiovascular risk factors (age ≥ 55 years for men or ≥ 60 years for women and one or more of dyslipidemia, hypertension, or current smoking) or established cardiovascular disease.

Among the 17,160 randomized patients, 6,974 (40.6%) had established cardiovascular disease and 10,186 (59.4%) had no established cardiovascular disease. 8,582 patients were randomized to dapagliflozin 10 mg and 8,578 to placebo and were followed for a median of 4.2 years.

The mean age of the study population was 63.9 years, 37.4% were female. Overall, 22.4% had diabetes for ≤ 5 years, and the mean duration of diabetes was 11.9 years. The mean HbA1c was 8.3% and the mean body mass index was 32.1 kg/m2.

At baseline, 10.0% of patients had a history of heart failure. The mean eGFR was 85.2 mL/min/1.73 m2, 7.4% of patients had an eGFR < 60 mL/min/1.73 m2, and 30.3% of patients had micro- or macroalbuminuria (urinary albumin/creatinine ratio [UACR] ≥ 30 to ≤ 300 mg/g or > 300 mg/g, respectively).

Most patients (98%) were using one or more diabetes medications at baseline, including metformin (82%), insulin (41%), and sulfonylurea (43%).

The primary composite endpoints were time to first occurrence of any of the following events: cardiovascular death, myocardial infarction, or ischemic stroke (major adverse cardiovascular events [MACE]), and time to first event including hospitalization for heart failure or cardiovascular death. Secondary endpoints were the renal composite endpoint and death from any cause.

Dapagliflozin 10 mg demonstrated non-inferiority versus placebo for outcomes such as cardiovascular death, myocardial infarction, or ischemic stroke (one-sided p < 0.001).

Heart failure or cardiovascular death

Dapagliflozin 10 mg demonstrated superiority versus placebo in preventing hospitalization for heart failure or cardiovascular death. The difference in treatment effect was due to hospitalization for heart failure with no difference in cardiovascular death.

The benefit of dapagliflozin treatment compared with placebo was observed in both patients with and without established cardiovascular disease, with and without heart failure at baseline, and was consistent across subgroups, including age, gender, renal function (eGFR), and region.

The superiority of dapagliflozin over placebo was not demonstrated for MACE (p = 0.172). The renal composite endpoint and death from any cause were not tested as part of the confirmatory testing procedure.

Nephropathy

Dapagliflozin reduced the incidence of the composite endpoint of confirmed persistent decline in eGFR, end-stage renal disease (ESRD), and death from renal or cardiovascular disease. The difference between groups was due to a reduction in the renal component events of persistent decline in eGFR, end-stage renal disease, and death from renal disease.

The hazard ratio for time to onset of nephropathy (persistent decline in eGFR, CKD, and death from renal disease) was 0.53 (95% CI 0.43; 0.66) for dapagliflozin compared with placebo.

In addition, dapagliflozin reduced new episodes of persistent albuminuria (HR 0.79 [95% CI 0.72, 0.87]) and resulted in greater regression of macroalbuminuria (HR 1.82 [95% CI 1.51, 2.20]) compared with placebo.

Heart failure

The Dapagliflozin Prevention of Adverse Events in Heart Failure (DAPA-HF) trial was an international, multicenter, randomized, double-blind, placebo-controlled trial in patients with heart failure (New York Heart Association [NYHA] functional class II–IV) and reduced ejection fraction (left ventricular ejection fraction [LVEF] ≤ 40%). The objective of this study was to determine the effect of dapagliflozin compared to placebo when added to standard of care on the incidence of cardiovascular death and worsening of heart failure.

Of the 4744 patients, 2373 were randomized to dapagliflozin 10 mg and 2371 to placebo, with a median follow-up of 18 months. The mean age of the study population was 66 years, and 77% were male.

At baseline, 67.5% of patients were in NYHA class II, 31.6% in class III, and 0.9% in class IV, with a mean LVEF of 32%, 56% of heart failure cases were ischemic, 36% nonischemic, and 8% of unknown etiology. In each treatment group, 42% of patients had a history of type 2 diabetes, and 3% of patients in each group were classified as having type 2 diabetes based on an HbA1c ≥ 6.5% at both baseline and randomization. Patients received standard of care; 94% of patients were treated with an ACE inhibitor, ARB, or an angiotensin receptor/neprilysin inhibitor (ARNI, 11%), 96% with a beta-blocker, 71% with a mineralocorticoid receptor antagonist (MRAs), 93% with a diuretic, and 26% had an implanted device (with defibrillator function).

Patients with an eGFR ≥ 30 mL/min/1.73 m2 at baseline were enrolled. The mean eGFR was 66 mL/min/1.73 m2, 41% of patients had an eGFR < 60 mL/min/1.73 m2, and 15% of patients had an eGFR < 45 mL/min/1.73 m2.

Cardiovascular death and worsening heart failure

Dapagliflozin was superior to placebo in preventing the primary composite endpoint of cardiovascular death, hospitalization for heart failure, or emergency department visit for heart failure (HR 0.74 [95% CI 0.65; 0.85], p < 0.0001). The effect was observed early and was maintained throughout the study (Figure 1).

Figure 1. Time to first occurrence of cardiovascular death, hospitalization for heart failure, or emergency department visit for heart failure

An emergency department visit for heart failure was defined as an urgent, unscheduled visit to a physician, such as in an emergency department, and the need for treatment for worsening heart failure (other than simply increasing oral diuretics).

Patients at risk is the number of patients who are at risk at the beginning of the period.

All three components of the primary composite endpoint individually contributed to the treatment effect (Figure 2). Fewer emergency department visits for heart failure were recorded.

An emergency department visit for heart failure was defined as an urgent, unscheduled visit to a physician, such as in an emergency department, and the need for treatment for worsening heart failure (other than simply increasing oral diuretics).

The number of first events for individual components is the actual number of first events for each component and is not added to the number of events in the combined endpoint.

Event rates are presented as the ratio of the number of participants with events per 100 patient-years of follow-up.

p-values for individual components and all-cause mortality are nominal.

Dapagliflozin also reduced the total number of hospitalizations for heart failure (primary and secondary) and cardiovascular death; 567 cases were reported in the dapagliflozin group compared with 742 cases in the placebo group (hazard ratio 0.75 [95% CI 0.65, 0.88]; p = 0.0002).

The benefit of dapagliflozin treatment was observed in patients with heart failure with and without type 2 diabetes. Dapagliflozin reduced the primary composite endpoint of cardiovascular death and worsening heart failure with a HR of 0.75 (95% CI 0.63; 0.90) in patients with diabetes and 0.73 (95% CI 0.60; 0.88) in patients without diabetes.

The benefit of dapagliflozin treatment compared with placebo on the primary endpoint was also observed in other key subgroups, including those with concomitant heart failure treatment, renal function (eGFR), and subgroups by age, gender, and region.

Patient-reported treatment outcomes — heart failure symptoms

The effect of dapagliflozin on heart failure symptoms was assessed using the Kansas Cardiomyopathy Symptom Score (KCCQ-TSS), which measures the frequency and severity of heart failure symptoms, including fatigue, peripheral edema, dyspnea, and orthopnea. Scores range from 0 to 100, with higher scores indicating better health.

Treatment with dapagliflozin had a statistically and clinically significant advantage over placebo in heart failure symptoms, as measured by change from baseline at month 8 on the KCCQ-TSS (odds ratio 1.18 [95% CI 1.11, 1.26]; p < 0.0001). The results took into account the frequency and severity of symptoms. The advantage was observed in both improving heart failure symptoms and preventing worsening of heart failure symptoms.

In the analyses of respondent responses, the proportion of patients with clinically meaningful improvement in the KCCQ-TSS at 8 months from baseline, defined as 5 points or more, was higher in the dapagliflozin group compared to the placebo group. The number of patients with clinically meaningful worsening, defined as 5 points or more, was lower in the dapagliflozin group compared to the placebo group. The benefits observed with dapagliflozin were maintained when using more conservative cutoffs for larger clinically meaningful changes (Table 5).

Table 5. Number and percentage of patients with clinically significant improvement and worsening after 8 months on the KCCQ-TSS

Change in initial assessment after 8 months	Dapagliflozin 10 mg n.a. = 2086	Placebo n.a. = 2062
Improvement	n (%) improvementb	n (%) improvementb	Risk ratioc (95% CI)	p-valuef
≥ 5 points	933 (44.7)	794 (38.5)	1.14 (1.06; 1.22)	0.0002
≥ 10 points	689 (33.0)	579 (28.1)	1.13 (1.05; 1.22)	0.0018
≥ 15 points	474 (22.7)	406 (19.7)	1.10 (1.01; 1.19)	0.0300
Deterioration	n (%) deteriorationd	n (%) deteriorationd	Hazard ratio (95% CI)	p-valuef
≥ 5 points	537 (25.7)	693 (33.6)	0.84 (0.78; 0.89)	<0.0001
≥ 10 points	395 (18.9)	506 (24 Specifications Characteristics Active ingredient Dapagliflozin Adults Can ATC code A DIGESTIVE SYSTEM AND METABOLISM AGENTS; A10 ANTIDIABETIC DRUGS; A10B HYPOGLYCAEMISING DRUGS, EXCEPT INSULINS; A10B K Sodium-glucose cotransporter 2 inhibitors; A10B K01 Dapagliflozin Country of manufacture Great Britain Diabetics Can Dosage 10 мг Drivers With caution For allergies With caution For children It is impossible. Form Film-coated tablets Method of application Inside, solid Nursing It is impossible. Pregnant It is impossible. Primary packaging blister Producer AstraZeneca Quantity per package 30 pcs Trade name Forksiga Vacation conditions By prescription Reviews There are no reviews for this product. + Add review Write a review Forxiga film-coated tablets 10 mg blister No. 30 My mark: Continue There are no reviews for this product, be the first to leave your review. Answers & questions Add your question and we will answer as soon as possible. + Ask a question Ask a question Add your question and we will answer as soon as possible. * Your question Continue No questions about this product, be the first and ask your question. You are watched new Hit Renial film-coated tablets 50 mg blister No. 30 In stock 0 936.87 грн. Add to Cart new Hit Phyto-ear drops for adults No. 2 In stock 0 174.66 грн. Add to Cart new Hit Medical plaster leopad 5 cm x 7.5 cm with silver ions No. 1 In stock 0 34.30 грн. Add to Cart new Hit Hydrofemin plus vaginal gel tube 75 g In stock 0 695.02 грн. Add to Cart new Hit Ursonost capsules 300 mg No. 50 In stock 0 1 192.84 грн. Add to Cart new Hit Exemestane-Vista AC film-coated tablets 25 mg No. 30 In stock 0 1 038.01 грн. Add to Cart new Hit Augmentin film-coated tablets 500 mg + 125 mg blister No. 14 In stock 0 469.22 грн. Add to Cart new Hit Crazy Bombs Kids Starfish Bath Bomb 120 g In stock 0 155.80 грн. Add to Cart new Hit Vichy Homme Shaving Gel Cream for Sensitive Skin 150 ml In stock 0 760.76 грн. Add to Cart new Hit AEROSKIN Biolikar aerosol liquid waterproof patch 50 ml In stock 0 289.10 грн. Add to Cart 1 072.70 грн. Add to Cart