Before starting treatment with IDegLira, this real-world population of mostly insulin-experienced (91.9%) Swiss patients had a longer duration of diabetes (12.5 years), poorer glucose control (HbA1c 9.2%), and greater mean body weight (96.5 kg) compared with patients enrolled in randomized trials of a comparable duration of follow-up (26–52 weeks) [11, 13, 14].
As was reported in the randomized clinical trials of IDegLira, in this follow-up of Swiss patients with T2D of relatively long duration, mean HbA1c decreased after approximately 26 weeks of treatment. The reduction in HbA1c in these poorly controlled patients (−1.7%) was of a slightly lesser extent than those reported from the more restricted patient populations enrolled in randomized, treat-to-target trials (−1.8% to −1.9%) [11, 13, 14]. Furthermore, the improvement in HbA1c in the Swiss patients was detectable at approximately 12 weeks (Fig. 1a), which is consistent with data from randomized clinical trials . Unfortunately, as there were no observations in the period between switching to IDegLira and 12 weeks, it is not possible to determine precisely when the decrease began. These results are also consistent with a post hoc analysis of two randomized controlled trials, which showed that the reduction in HbA1c was largely independent of disease duration or previous insulin dose . By comparison, the reduction in weight among those patients completing follow-up (−1.9 kg) in this study was greater than that reported in two randomized trials, −0.5 kg  and −1.4 kg , but less than that reported for another trial (−2.7 kg ).
It should be mentioned that, very often, a seasonal weight variation is observed, with an increase during winter and a decrease during summer. Despite the fact that the 6-month observation period for these patients went from the beginning of winter to spring, there was a trend towards weight loss.
The decrease in systolic blood pressure in these patients (9.1 mmHg) is also consistent with results from randomized trials of liraglutide alone  and IDegLira .
The absence of any episodes of severe hypoglycemia is consistent with previously reported randomized trials of IDegLira in patients previously treated with insulin [13, 14]. In these larger-scale studies, only one episode of severe hypoglycemia was reported and this occurred during exercise (mountain climbing) and was resolved after consumption of a sweet beverage .
Among the limitations of this study is the small sample size. This was fixed on the basis of the constraint of the observation period. For the chosen observation period, the number of patients included is representative of the volume of consultations performed by a private practice in a Swiss city. A longer period of observation would probably have better consolidated the data but it would have required a longer period and a greater workforce so as not to interfere with the usual functioning of the private practice. Data on adverse events such as hypoglycemia were not systematically solicited, nor were reported events assessed. Instead, they were recorded only if patients mentioned them during a follow-up visit. However, patients were generally very open about their experience with IDegLira during follow-up visits.
Patients initiated therapy at a higher dose of IDegLira (20 dose steps for insulin experienced, 16 dose steps for insulin naïve) than is recommended in the IDegLira prescribing information (16 dose steps for insulin experienced and 10 dose steps when transferring from oral therapy) . This shows how clinical practice in a real-world setting differs from clinical trials. In a clinical trial, where patients are monitored closely and regularly, titration can be slower, and frequent contact with participants can be helpful in ensuring treatment compliance. In real-life practice, where visits and follow-up are much less frequent, it may be necessary to be more aggressive in the titration process so that patients sense improvement and therefore retain the motivation to continue with treatment. The trade-off for starting with a higher dose of IDegLira, of course, may be in the inability of some patients to continue therapy because of gastrointestinal side effects. Given the lower body weight among patients who discontinued in this follow-up study, a more individualized titration schedule might be warranted, taking into account factors such as body weight. Despite the starting dose of IDegLira in this study being higher than that recommended, patients’ total insulin requirements were nevertheless reduced from those at baseline over 6 months, with the achievement of an improved and acceptable mean HbA1c. Had a treat-to-target approach been used, it is likely that HbA1c could have been further reduced.
Some aspects of diabetes treatment, which are just as important as glycemic control, have not been formally evaluated in this observational analysis, but deserve to be mentioned here. According to patients’ feedback, the process of changing treatment to IDegLira was itself helpful by increasing their motivation to better manage their diabetes. Examples include being more careful about what they eat and when, and engaging in more frequent self-measured blood glucose testing. This in turn has an impact on improving glycemia. For some patients, concurrent stressful life events (e.g., serious illness in a spouse, divorce) may have interfered with optimal diabetes management. In others, while switching treatment did not immediately result in improvements in glycemic control, there were nevertheless important benefits with respect to quality of life (e.g., being able to engage in more regular exercise owing to feeling less sick).