2018 Clinical Practice Guidelines

Pharmacologic Glycemic Management of Type 2 Diabetes in Adults

Evidence is uncertain about the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and health outcomes in people with type 2 diabetes.

We aimed to assess the association between vitamin D status and all-cause mortality and cardiovascular disease in people with type 2 diabetes.

We did a systematic search in PubMed, Scopus, CENTRAL, and Web of Science until May 2022. We selected 1) cohort studies investigating the association between serum 25(OH)D concentration and mortality or cardiovascular disease in people with type 2 diabetes or prediabetes and 2) randomized trials of vitamin D supplementation in these patients. We used random-effects pairwise meta-analyses to calculate summary relative risks (RRs) and 95% confidence intervals (CI).

21 cohort studies and 6 randomized trials were included. Compared with sufficient vitamin D status (≥50 nmol/L), the RR of all-cause mortality was 1.36 (95% CI: 1.23, 1.49; n = 11 studies, GRADE = moderate) for vitamin D insufficiency (25 to <50 nmol/L), and 1.58 (1.33, 1.83; n = 16, GRADE = moderate) for deficiency (<25 nmol/L). Similar findings were observed for cardiovascular mortality and morbidity but not for cancer mortality. The certainty of evidence ranged from very low to moderate. Dose–response meta-analyses indicated nonlinear associations, with the lowest risk at 25(OH)D ∼60 nmol/L for all-cause and cardiovascular mortality. Supplementation with vitamin D did not reduce the risk of all-cause mortality (RR: 0.96, 95% CI: 0.79, 1.16; risk difference per 1000 patients: 3 fewer, 95% CI: 16 fewer, 12 more; n = 6 trials with 7316 participants; GRADE = low) or the risk of cardiovascular mortality and morbidity (very low- to low-certainty evidence).

Vitamin D deficiency and insufficiency are associated with a higher risk of all-cause and cardiovascular mortality in patients with type 2 diabetes or prediabetes. Vitamin D deficiency should be corrected in patients with type 2 diabetes to reach normal serum 25(OH)D concentrations, preferably 60 nmol/L.

This systemic review was registered at PROSPERO as CRD42022326429 (=https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=326429).

Diabetes is a major public health problem in Canada and requires multifactorial, consistent clinical management. The COVID-19 pandemic has increased challenges in the management of many chronic ailments, including diabetes. Diabetes was associated with a higher risk of severe illness in the context of COVID-19. Pandemic restrictions also impacted diabetes care continuity, which may have contributed to an increased risk of diabetes-related complications and mortality.

This was a retrospective cross-sectional study of prescription patterns of antihyperglycemic medications claimed by individuals with type 2 diabetes (T2D) before and during the COVID-19 pandemic using the IQVIA Canada Longitudinal Prescription Claims database. The study period was from March 1, 2018, to February 28, 2021. The study outcomes are described on a monthly, quarterly, and yearly basis and overall, and by medication, medication class, and insurance coverage type. “New-to-molecule” patients were defined as those claiming a medication during the analysis period that they had no history of claiming in the database. Adults with at least 1 year of prescription history available and claiming their first prescription for an antihyperglycemic drug during the analysis period were classified as newly diagnosed with T2D.

A similar number of people had at least 1 non-insulin antihyperglycemic prescription during the baseline, prepandemic, and pandemic periods in Canada (1,778,155, 1,822,403, and 1,797,272, respectively). However, the number of people initiating newer antihyperglycemic medications decreased at the beginning of the pandemic, in contrast to older medications, which remained consistent across the pandemic period. The number of people diagnosed with T2D decreased in the early months of the pandemic but recovered by October 2020.

The COVID-19 epidemic in Canada impacted clinical care for at-risk Canadians, with fewer being prescribed newer antihyperglycemic drugs and a reduction in the number of diagnoses of T2D.

Le diabète constitue un problème de santé publique important au Canada et exige une prise en charge clinique multifactorielle cohérente. La pandémie de COVID-19 a fait accroître les enjeux de la prise en charge de plusieurs maladies chroniques, y compris le diabète. Le diabète a été associé à un risque accru de maladies graves dans le contexte de la COVID-19. Les restrictions pandémiques qui ont aussi eu des répercussions sur la continuité des soins du diabète peuvent avoir contribué à une augmentation du risque de complications et de mortalité liées au diabète.

Cette étude transversale rétrospective qui portait sur les profils d’ordonnances d’antihyperglycémiants réclamés par les patients atteints du diabète de type 2 (DT2) avant et pendant la pandémie de COVID-19 reposait sur la base de données longitudinales sur les réclamations d’ordonnances d’IQVIA Canada. La période étudiée s’étendait du 1^er mars 2018 au 28 février 2021. Les résultats de l’étude sont dans l’ensemble décrits sur une base mensuelle, trimestrielle et annuelle, et par médicament, classe de médicaments et type de couverture d’assurance. Les patients qui avaient récemment commencé à prendre la molécule étaient définis comme suit : ceux qui avaient eu un médicament durant la période analysée et qui n’avaient eu aucun antécédent de réclamations selon la base de données. Les adultes qui avaient eu au moins 1 année d’ordonnances et qui avaient réclamé leur première ordonnance d’antihyperglycémiants durant la période analysée ont été classifiés dans le groupe des adultes qui avaient récemment reçu un diagnostic de DT2.

Un nombre similaire de personnes avaient eu au moins 1 ordonnance d’antihyperglycémiants non insuliniques durant les périodes initiale, prépandémique et pandémique au Canada (1 778 155, 1 822 403 et 1 797 272, et ce, respectivement). Toutefois, le nombre de personnes qui avaient commencé de nouveaux antihyperglycémiants avait diminué au début de la pandémie, contrairement aux anciens médicaments, qui étaient demeurés inchangés durant la période pandémique. Le nombre de personnes qui avaient reçu un diagnostic de DT2 avait diminué dans les premiers mois de la pandémie, mais s’était rétabli en octobre 2020.

L’épidémie de COVID-19 au Canada a eu des répercussions sur les soins cliniques des Canadiens à risque, c’est-à-dire un moins grand nombre d’ordonnances de nouveaux antihyperglycémiants et une réduction du nombre de diagnostics de DT2.

Combined polypharmacy treatments of multi-diseases like diabetes mellitus type 2 (DMT2) with its comorbidities could lead to serious adverse reactions (ADR) due to drug-drug interactions (DDIs). This study aimed to demonstrate that these DDI ADRs can be significantly reduced by carefully examining DDIs of recommended drugs and using advanced clinical decision support (CDS) tools, like PM-TOM (Personal Medicine: Therapy Optimization Method).

DMT2 with heart failure (HF) and atherosclerotic cardiovascular disease (ASCVD) were taken for analysis. First, 20 drug classes were selected, recommended in relevant medical guidelines (US, European and Canadian); for example, biguanides, sodium-glucose transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, insulins, angiotensin 2 receptor blockers, angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, diuretics, and statins. Next, these classes were combined into polypharmacy treatment cases, which were organized into three groups: Basic (combinations of three drug classes), Medial (five), and Advanced (eight). Then, the tool PM-TOM was used to find treatments with minimal and maximal drug interactions (MIN-DDI and MAX-DDI) for each case. Finally, these two treatments' minimal, average and maximal DDIs were calculated and statistically analyzed to examine the scope and effects of optimizing polypharmacy treatments in each case group.

In the Basic group, 16 polypharmacy treatment cases were created; in the Medial 210 and the Advanced 736. The MIN-DDI and MAX-DDI treatments in each case group showed significant DDI differences; for example, in the Basic group, the average DDI count in the MIN-DDI treatments was 0.19 and in the MAX-DDI ones 1.75, while in the Medial and Advanced groups, these indicators were 1.66 and 7.66, and 5.76 and 20.52, respectively. Also, 87% of optimized treatments (MIN-DDI) in the Basic group showed no DDIs, 37% in the Medial, and 9% in the Advanced. In addition, 70% of cases in the Medial group had at most two DDIs, and 49% in the Advanced group at most five.

These findings suggest that DDI ADRs in randomly selected (unoptimized) DMT2 polypharmacy treatments can be substantially reduced using specialized decision support tools, increasing patients' chances for successful treatment and decreasing health care costs. Similar findings can be expected for other multi-diseases as well.