Comparative risk of new-onset diabetes following commencement of antipsychotics in New Zealand: a population-based clustered multiple baseline time series design.

OBJECTIVE: Newer antipsychotics are increasingly prescribed off-label for non-psychotic ailments both in primary and secondary care settings, despite the purported risk of weight gain and development of type 2 diabetes mellitus. This study aims to determine any relationship between the development of clinically significant new-onset type 2 diabetes mellitus and novel antipsychotic use in New Zealand using hypnotic drugs as control. DESIGN: A population-based clustered multiple baseline time series design. SETTING: Routinely collected data from a complete national pharmaceutical database in New Zealand between 2005 and 2011. PARTICIPANTS: Patients aged 40-60 years in the year 2006 who were ever dispensed antipsychotics (exposure groups-first-generation antipsychotics, second-generation antipsychotics and antipsychotics with low, medium and high risk for weight gain) or hypnotics (control group) between 2006 and 2011. MAIN OUTCOME MEASURE: First ever metformin dispensed to patients in each study group between 2006 and 2011 as proxy for development of clinically significant type 2 diabetes mellitus, no longer amendable by lifestyle modifications. RESULTS: Patients dispensed a second-generation antipsychotic had 1.49 times increased risk (95% CI 1.10 to 2.03, p=0.011) of subsequently commencing metformin. Patients dispensed an antipsychotic with high risk of weight gain also had a 2.41 times increased risk of commencing on metformin (95% CI 1.42 to 4.09, p=0.001). CONCLUSIONS: Patients dispensed a second-generation antipsychotic and antipsychotics with high risk of weight gain appear to be at increased risk of being secondarily dispensed metformin. Caution should be taken with novel antipsychotic use for patients with increased baseline risk of type 2 diabetes mellitus.

The comparative risk of new-onset diabetes after prescription of drugs for cardiovascular risk prevention in primary care: a national cohort study.

OBJECTIVE: Recent studies suggest that statins increase the risk of subsequent diabetes with a clear dose response effect. However, patients prescribed statins have a higher background risk of diabetes. This national cohort study aims to provide an estimate of the comparative risks for subsequent development of new-onset diabetes in adults prescribed statins and in those with an already higher background risk on cardiovascular risk-modifying drugs and a control drug. DESIGN: Longitudinal cohort study. SETTING: Use of routinely collected data from a complete national primary care electronic prescription database in New Zealand. PARTICIPANTS: 32 086 patients aged between 40 and 60 years in 2005 were eligible and assigned to four non-overlapping groups receiving their first prescription for: (1) diclofenac (healthy population) n=7140; (2) antihypertensives thought likely to induce diabetes (thiazides and ß-blockers) n=5769; (3) antihypertensives thought less likely to induce diabetes (ACE inhibitors, angiotensin II receptor blockers, calcium channel blocker) n=6565 and (4) statins n=12 612. OUTCOME: Numbers of first metformin prescriptions were compared between these groups from 2006 to 2011. RESULTS: Patients prescribed statins have the highest risk of receiving a subsequent metformin prescription (HR 3.31; 95% CI 2.56 to 4.30; p<0.01), followed by patients prescribed antihypertensives thought less likely to induce diabetes (HR 2.32; 95% CI 1.74 to 3.09; p<0.01) and patients prescribed antihypertensives thought more likely to induce diabetes (HR 1.59; 95% CI 1.15 to 2.20; p<0.01) in the subsequent 6 years of follow-up, when compared to diclofenac. CONCLUSIONS: These findings further support the link between statin use and new-onset diabetes and suggest that the understanding of diabetes risk associated with different antihypertensive drug classes may bear practice modification. This provides important information for future research, and for prescribers and patients when considering the risks and benefits of different types of cardiovascular risk-modifying drugs.