A 54-year-old man comes to the office for follow-up of type 2 diabetes mellitus. The patient also has a history of hypertension, obesity, and chronic kidney disease (CKD). Medications include an antihyperglycemic agent and insulin. Blood pressure is 148/92 mm Hg and pulse is 81/min and regular. BMI is 34 kg/m². Physical examination is otherwise unremarkable. Laboratory results are as follows: Based on his serum creatinine level, his CKD has progressed, and the calculated glomerular filtration rate (eGFR) is now 42 mL/min/1.73 m², down from 55 mL/min/1.73 m² as measured 6 months ago. Based on the ad, which of the following is the most accurate statement concerning the use of kanebaflozin in this patient? A)Adding kanebaflozin 300 mg will increase by 0.46% the patient's probability of lowering mean A1c B)Because his A1c is 8.0%, the patient would likely benefit more from 100 mg than 300 mg of kanebaflozin C)Either dose of kanebaflozin will likely lead to a statistically significant reduction in the patient's mean A1c level D)The patient is unlikely to derive any significant benefit from kanebaflozin due to the decline in kidney function E)The study was underpowered to detect any statistically significant benefit from kanebaflozin

Question

Quizplus · Accepted Answer

Explanation: 11ec2b69_c0fc_3fbe_8f63_0be2593c2010_MD0005_00 The study described in the drug ad compared the effect of adding kanebaflozin in different dosages to current diabetes treatment in patients with moderate renal impairment limits (ie, eGFR 30 to <50 mL/min/1.73 m²) that were inadequately controlled by their current treatment. The primary endpoint was the changes in A1c from baseline to week 26. Secondary endpoints included change in fasting plasma glucose, proportion of subjects reaching A1c <7.0%, and renal safety parameters (eg, eGFR). The difference in adjusted mean A1c for kanebaflozin was −0.39% (−0.58, −0.07) with 100 mg and −0.51% (−0.71, −0.14) with 300 mg of the drug (each compared to placebo). Given that both values are negative and neither confidence interval (CI) includes the null value (ie, 0), both treatment groups showed a statistically significant decrease in A1c when compared to placebo. The CIs overlap over the range (−0.58, −0.14). When CIs of means or proportions for ≥2 groups do not overlap, it is always correct to establish a statistically significant difference between the groups. However, when CIs overlap, there may or may not be a statistically significant difference between the groups. Therefore, both 100 mg and 300 mg doses of kanebaflozin led to a statistically significant decrease in A1c compared to placebo; however, the fact that the CIs overlap means that there may or may not be a statistically significant difference between the 100 mg and the 300 mg doses (ie, either dose is likely to help). (Choice A) Adding kanebaflozin 300 mg reduced the adjusted mean A1c by −0.46% compared to placebo; this value does not reflect the probability of lowering mean A1c. (Choice B) Although the patient had a mean baseline A1c value (ie, 8.0%) equal to the mean baseline A1c value for the group receiving kanebaflozin 100 mg, a higher benefit for the patient at this dosage is not guaranteed. A statistically significant difference (ie, reduction in mean A1c) between the 100 mg and 300 mg doses of kanebaflozin could not be established. (Choice D) The patient's kidney function declined from 55 mL/min/1.73 m² to 42 mL/min/1.73 m² within a period of 6 months. However, the patient's kidney function is still within the limits (ie, eGFR 30 to <50 mL/min/1.73 m²) established for kanebaflozin treatment. Therefore, adding kanebaflozin to the current treatment will likely be significantly beneficial for the patient. (Choice E) Statistical power is the probability of finding a statistically significant difference (ie, effect from treatment) when one exists. Any randomized efficacy trial must have adequate power to evaluate the primary endpoint (eg, change in A1c at 26 weeks). In this study, both treatment groups showed a statistically significant decrease in A1c when compared to placebo, suggesting that the study was appropriately powered. Educational objective: Nonoverlapping confidence intervals always imply a statistically significant difference between groups. However, the opposite is not necessarily true.

A 54-Year-Old Man Comes to the Office for Follow-Up of Type