Efficacy and safety of linagliptin to improve glucose control in older people with type 2 diabetes on stable insulin therapy: A randomized trial.

AIM: To assess the addition of linagliptin as an alternative to insulin uptitration in older people with type 2 diabetes on stable insulin therapy. MATERIALS AND METHODS: This phase 4, randomized, multicentre, double-blinded, placebo-controlled, 24-week study recruited individuals on stable insulin, with baseline HbA1c 7.0%-10.0%, aged ≥60 years and body mass index ≤45 kg/m2 . HbA1c and fasting plasma glucose were measured at study visits, and participants assessed glycaemic control with a self-monitoring blood glucose device. Adverse events (AEs) were reported during the study. RESULTS: Three hundred and two participants were randomized 1:1 to linagliptin 5 mg qd and placebo, with one third of patients from Japan. Study population age and HbA1c (baseline mean ± SD) were 72.4 ± 5.4 years and 8.2 ± 0.8%, respectively; ~80% of participants were aged ≥70 years; 80% had macrovascular complications, one third had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 ; and half had been diagnosed with diabetes for >15 years. Linagliptin significantly improved glucose control at 24 weeks (HbA1c-adjusted mean change vs. placebo: -0.63%; P <0.0001) and the probability of achieving predefined HbA1c targets without hypoglycaemia (HbA1c <8.0%: OR 2.02; P <0.05 and HbA1c <7.0%: OR 2.44; P <0.01). Linagliptin versus placebo was well tolerated, with similar incidences of AEs, including clinically important hypoglycaemia (blood glucose <54 mg/dL) or severe hypoglycaemia. CONCLUSIONS: Addition of linagliptin improves glucose control without an excess of hypoglycaemia in older patients with type 2 diabetes on stable insulin therapy.

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5-12.0% were randomized to double-blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end-point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries. RESULTS: After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was -2.99 ± 0.18% with linagliptin/metformin and -1.84 ± 0.18% with linagliptin; a treatment difference of -1.15% (95% confidence interval -1.65 to -0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was -0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference -1.78 kg [95% confidence interval -2.99 to -0.57, P = 0.0043]). Drug-related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations. CONCLUSIONS: In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia.

OBJECTIVES: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. METHODS: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. RESULTS: HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% ± 0.12% with linagliptin/metformin (n = 132) and -2.02% ± 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to -0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference -0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. CONCLUSION: Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT01512979.

Validity of the decreased sexual desire screener for diagnosing hypoactive sexual desire disorder.

The decreased sexual desire screener is a brief diagnostic instrument for generalized acquired hypoactive sexual desire disorder in women. During the screening visit of 2 clinical trials, the authors assessed sensitivity of the decreased sexual desire screener in premenopausal women presenting with decreased sexual desire. The authors compared diagnoses of generalized acquired hypoactive sexual desire disorder made by clinicians who were not trained or specialized in the diagnosis of female sexual dysfunction using the decreased sexual desire screener with diagnoses made by expert clinicians after an extensive diagnostic interview. The sensitivity of the decreased sexual desire screener was 0.946 in a North American trial and 0.960 in a European trial.

eDiary and Female Sexual Distress Scale(©) in evaluating distress in hypoactive sexual desire disorder (HSDD).

Sex-related distress is integral to the diagnosis of hypoactive sexual desire disorder (HSDD). This article describes the results of three prospective, non-treatment validation studies (two North American and one European), each testing over 200 participants with HSDD, other types of female sexual dysfunction (FSD), or no FSD in which the 12-item Female Sexual Distress Scale(©) (FSDS(©)), the 13-item FSDS-Revised(©)(FSDS-R(©)), and a single question asked using a daily electronic diary (the eDiary For HSDD Trials(©); eDiary) were used to measure sex-related distress. FSDS results with 30- and seven-day recall were equivalent. The results observed with FSDS-R Item 13 (a single question assessing concern due to low sexual desire) were comparable to the FSDS. Mean eDiary monthly distress scores were closer to the minimum possible score (equivalent to "a little bit" of distress) and were about twice as variable as FSDS or FSDS-R Item 13 scores in participants with HSDD. All three measures confirmed that there is more distress in women with HSDD compared to women with no sexual dysfunction at all time points, demonstrating discriminant validity.

Validation of the sexual interest and desire inventory-female in hypoactive sexual desire disorder.

INTRODUCTION: The Sexual Interest and Desire Inventory-Female (SIDI-F) is a 13-item scale developed as a clinician-administered assessment tool to measure hypoactive sexual desire disorder (HSDD) severity in women. AIM: To estimate the reliability and validity of the SIDI-F as a measure of HSDD severity. METHODS: Women, aged 18-65 years, with primary HSDD, Female Sexual Arousal Disorder (FSAD), or no Female Sexual Dysfunction (no FSD) participated in two nontreatment studies (in North America and Europe). On days 0 and 28, subjects were assessed using the SIDI-F, Female Sexual Function Index (FSFI), Changes in Sexual Functioning Questionnaire-Female (CSFQ-F), Locke-Wallace Marital Adjustment Test (MAT) and the Female Sexual Distress Scale (FSDS). MAIN OUTCOME MEASURES: Discriminant validity, convergent validity, divergent validity, test-retest validity, and internal consistency of the SIDI-F. RESULTS: The North American study enrolled women with HSDD (N = 113), FSAD (N = 49) and no FSD (N = 61); the European study enrolled women with HSDD (N = 130) and no FSD (N = 124). In both studies, mean SIDI-F total score for women with HSDD was lower than for those with no FSD (P < 0.001, for all) demonstrating discriminant validity. Further, mean SIDI-F total score for women with HSDD was lower than for those with FSAD in the North American study (P < 0.001). Convergent validity with the FSFI and CSFQ-F and divergent validity with MAT were demonstrated. Test-retest reliability and internal consistency were high. CONCLUSIONS: The SIDI-F is a valid and reliable measure of HSDD severity in women.

Cutoff score of the sexual interest and desire inventory-female for diagnosis of hypoactive sexual desire disorder.

OBJECTIVE: To determine the most appropriate cutoff value for the Sexual Interest and Desire Inventory-Female (SIDI-F) score to discriminate between women with hypoactive sexual desire disorder (HSDD) and those with no female sexual dysfunction (FSD). The SIDI-F is a clinician-rated instrument consisting of 13 items designed to assess HSDD severity in women. The total score ranges from 0 to 51, with higher scores indicating better sexual function. METHODS: Data from patients enrolled in a North American nontreatment study and a European nontreatment study were analyzed. Both studies were 4-week, prospective, multicenter trials designed to assess the reliability and validity of the SIDI-F. Only patients with HSDD or no FSD were included in this analysis. Receiver operating characteristics (ROC) analysis was used to determine the ability of the SIDI-F to differentiate between patients with HSDD and those with no FSD at baseline. RESULTS: A total of 428 women were included in this analysis: 174 from North America (HSDD 113, no FSD 61) and 254 from Europe (HSDD 130, no FSD 124). In the North American study, a SIDI-F cutoff score of 33 minimized the difference between sensitivity (94.7%) and specificity (93.4%). In the European study, SIDI-F cutoff scores of both 33 and 34 minimized the difference between sensitivity (95.2%) and specificity (94.4%). CONCLUSIONS: In appropriately screened women, a SIDI-F score of ≤33 indicates the presence of HSDD.

Validation of the decreased sexual desire screener (DSDS): a brief diagnostic instrument for generalized acquired female hypoactive sexual desire disorder (HSDD).

INTRODUCTION: An accurate diagnosis of Hypoactive Sexual Desire Disorder (HSDD) currently relies on a time-consuming interview with an expert clinician. Limited access to such expertise means that many women with HSDD remain undiagnosed. The Decreased Sexual Desire Screener (DSDS) was developed to provide clinicians who are neither trained nor specialized in Female Sexual Dysfunction (FSD) with a brief diagnostic procedure for the diagnosis of generalized acquired HSDD in women. METHODS: A prospective non-treatment multicenter study enrolled 263 women at 27 centers in North America in order to test the validity of the DSDS for diagnosing generalized acquired HSDD in women. Subjects completed the DSDS at the screening visit and their answers were reviewed with a clinician who was not an expert in FSD ("non-expert clinician"). Separately and while being unaware of the non-expert clinician's diagnosis, an expert clinician conducted a standard diagnostic interview. MAIN OUTCOME MEASURES: Diagnostic outcomes (generalized acquired HSDD or not) were compared. Primary endpoints included the sensitivity and specificity of the DSDS relative to the standard diagnostic interview. Subject and non-expert clinician debriefing were obtained via a written, structured interview. This ensured that a large sample could be tested under uniform conditions across multiple sites. RESULTS: Diagnostic assessment by DSDS and standard diagnostic interview were in agreement in 85.2% (224/263) of cases, with the sensitivity and specificity of the DSDS 83.6% and 87.8%, respectively. Debriefing showed that the five DSDS questions were well understood by 85.4% (76/89) of subjects included in the debriefing exercise, while non-expert clinicians considered the DSDS questions adequate to diagnose HSDD in 92.9% (235/253) of cases. CONCLUSIONS: The DSDS is a sensitive and specific brief diagnostic instrument for generalized acquired HSDD in women that is quick and easy to use.

Validation of the female sexual distress scale-revised for assessing distress in women with hypoactive sexual desire disorder.

INTRODUCTION: The concept of sexually related personal distress is currently central to the diagnosis of all female sexual dysfunctions (FSD). In the current study, we have focused on validating a slightly revised version of the Female Sexual Distress Scale (FSDS), the FSDS-Revised (FSDS-R), to enhance the sensitivity of the instrument with patients suffering from hypoactive sexual desire disorder (HSDD). In addition, we have attempted to extend the validation generalizability of the scale by demonstrating that both instruments possess reliability and discriminative validity in premenopausal women with HSDD. AIM: To assess the validity of the revised version of the FSDS, the FSDS-R, for measuring sexual distress in women with HSDD. METHODS: A prospective methodological study carried out at 27 centers in North America enrolled 296 women aged 18-50 years with HSDD, another female sexual dysfunction (FSD), or no FSD. The subjects completed the FSDS-R at baseline, day 7, and day 28, with a 30-day recall at baseline and with a 7-day recall on days 7 and 28. MAIN OUTCOME MEASURES: Receiver operating characteristic (ROC) analyses of FSDS, FSDS-R, and FSDS-R item 13 were used for the differentiation of HSDD from no FSD, while intraclass correlation coefficient (ICC) was used to estimate test-retest reliability. Cronbach's coefficient alpha was used to measure the internal consistency of the FSDS-R and Pearson's correlation coefficient to assess FSDS, FSDS-R, and FSDS-R item 13 with different recall periods (7 and 30 days). RESULTS: Mean total FSDS, FSDS-R, and FSDS-R item 13 scores with either recall period were significantly higher (P < 0.0001) in women with FSD or HSDD than in women with no FSD, showing both tests had discriminant validity. ROC analysis confirmed these findings, while an ICC of >0.74 showed the test-retest reliability of both scales, including FSDS-R item 13 alone, and Cronbach's coefficient alpha of >0.86 confirmed the internal consistency of both tests. CONCLUSIONS: Consistent with the FSDS, the FSDS-R demonstrated good discriminant validity, high test-retest reliability, and a high degree of internal consistency in measuring sexually related personal distress in women with HSDD. FSDS-R item 13 alone also demonstrated good discriminant validity and test-retest reliability.

Reliability and validity of the Sexual Interest and Desire Inventory-Female (SIDI-F), a scale designed to measure severity of female hypoactive sexual desire disorder.

The Sexual Interest and Desire Inventory-Female (SIDI-F) is a 13-item scale developed as a clinician-administered assessment tool to quantify the severity of symptoms in women diagnosed with hypoactive sexual desire disorder (HSDD). The present investigation assessed the reliability and validity of the SIDI-F as a measure of HSDD severity. Results show that the SIDI-F exhibits excellent internal consistency, with Cronbach's alpha of 0.9. The validity of the SIDI-F as a measure of HSDD severity was confirmed by a number of observations. Women with a clinical diagnosis (Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR; American Psychiatric Association, 2000]) of HSDD had significantly lower SIDI-F scores than women not meeting diagnostic criteria for any subtype of female sexual dysfunction and women diagnosed with female orgasmic disorder. There was a high correlation between scores on the SIDI-F and scores on the Female Sexual Function Index (FSFI; Rosen et al., 2000) and an interactive voice response version of the Changes in Sexual Functioning Questionnaire (CSFQ; Clayton, McGarvey, & Clavet, 1997; Clayton, McGarvey, Clavet, & Piazza, 1997), two validated measures that assess general female sexual dysfunction. In contrast, there was a poor correlation between SIDI-F scores and scores on a slightly modified Marital Adjustment Scale (Locke, Wallace, 1959; MAS), an assessment of general (nonsexual) relationship satisfaction. Taken together, the results of the present investigation indicate that the SIDI-F is a reliable and valid measure of HSDD severity, independent of relationship issues.