scholarly journals Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e034613
Author(s):  
Kamlesh Khunti ◽  
Marilia B Gomes ◽  
Mikhail Kosiborod ◽  
Antonio Nicolucci ◽  
Stuart Pocock ◽  
...  

ObjectivesTo evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.DesignDISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019.SettingPrimary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations.ParticipantsA total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy.Primary and secondary outcome measuresThe proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change.ResultsOf the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe.ConclusionsA substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes.Trial registration numbersNCT02322762 and NCT02226822.

2019 ◽  
Vol 7 (1) ◽  
pp. e000627 ◽  
Author(s):  
Stéphane Pintat ◽  
Peter Fenici ◽  
Niklas Hammar ◽  
Linong Ji ◽  
Kamlesh Khunti ◽  
...  

ObjectiveTo assess the eligibility of patients participating in DISCOVER (a 3-year, prospective, observational study program of 15 992 patients with type 2 diabetes [T2D] initiating a second-line glucose-lowering therapy across 38 countries) for four cardiovascular outcomes trials (CVOTs) of sodium–glucose cotransporter 2 inhibitors (CANagliflozin cardioVascular Assessment Study [CANVAS], Dapagliflozin effect on CardiovascuLAR Events trial [DECLARE-TIMI 58], EMPAgliflozin cardiovascular OUTCOME event trial [EMPA-REG OUTCOME], and eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial [VERTIS-CV]).Research design and methodsIn this cross-sectional analysis, baseline characteristics of DISCOVER patients were compared with the inclusion and exclusion criteria of the CVOTs to assess patient eligibility, overall and in four regions (Asia-Pacific, Europe, Latin America, and Middle East and Africa).ResultsOverall, 11 385 patients (71.2%) had sufficient data for the analysis; 56.1% were men. The mean age and time since T2D diagnosis were 57.4 and 5.6 years, respectively. The mean glycated hemoglobin level was 8.3%. DISCOVER patients were younger, and fewer had a history of cardiovascular disease, than those enrolled in the CVOTs. Eligibility varied across the CVOTs; the proportion of eligible DISCOVER patients was highest for DECLARE-TIMI 58 (40.5%), followed by CANVAS (19.9%), VERTIS-CV (7.2%), and EMPA-REG OUTCOME (7.1%); 54.6% of patients were not eligible for any CVOT. Eligibility for each CVOT varied across regions, which was explained by the differing proportions of patients with established cardiovascular disease.ConclusionsIn a large, international population of patients with T2D initiating a second-line glucose-lowering therapy, DECLARE-TIMI 58 was the most inclusive CVOT, suggesting that its study population will be more representative of patients encountered in routine clinical practice than those of CANVAS, EMPA-REG OUTCOME, and VERTIS-CV.


Author(s):  
Brenda Bongaerts ◽  
Bianca Kollhorst ◽  
Oliver Kuss ◽  
Iris Pigeot ◽  
Wolfgang Rathmann

Abstract Aims To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. Materials and methods Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. Results A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. Conclusions Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.


2020 ◽  
Vol 165 ◽  
pp. 108250
Author(s):  
Wolfgang Rathmann ◽  
Bernard Charbonnel ◽  
Marília B. Gomes ◽  
Niklas Hammar ◽  
Kamlesh Khunti ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Antoine Christiaens ◽  
Benoit Boland ◽  
Marie Germanidis ◽  
Olivia Dalleur ◽  
Séverine Henrard

Abstract Background Glucose-lowering therapy (GLT) should be individualized in older patients with type 2 diabetes (T2D) according to their health status and their life expectancy. This study aimed at assessing the inappropriateness of GLT prescribing and the one-year mortality rate in geriatric patients with T2D. Methods Retrospective cohort study of consecutive inpatients with T2D admitted to a geriatric ward of a Belgian university hospital. Inclusion criteria were age ≥ 75 years, T2D with GLT before admission, and HbA1c measurement during the hospital stay. Comorbidities and geriatric syndromes were collected. GLT agents were classified into hypoglycaemic and non-hypoglycaemic ones, and their dosages were expressed in daily defined dose (DDD). Health status (intermediate or poor) and GLT appropriateness (appropriate, overtreatment, undertreatment) were assessed according to the 2019 Endocrine Society guideline on diabetes treatment in older adults, in which GLT overtreatment requires the presence of hypoglycaemic therapy. One-year mortality was determined using the National Registry of vital status, and its associated factors were analysed using multivariable Cox’ regression. Results The 318 geriatric patients with T2D (median age 84 years; 46% female) were in intermediate (33%) or poor health (67%). These two groups reached similar low HbA1c values (median 6.9%) with similar GLT regimens. GLT overtreatment was frequent (57%) irrespectively of the geriatric features. One-year mortality rate was high (38.5%) and associated in multivariate analysis with poor health status (HR: 1.59, p = 0.033), malnutrition (HR: 1.67, p = 0.006) and GLT overtreatment (HR: 1.73, p = 0.023). Patients with GLT overtreatment had a higher mortality rate (44.5%). Conclusions GLT overtreatment was present in more than half of these geriatric patients. Many of them were in poor health status and died within one-year. Special attention should be paid to individualisation of the HbA1c goals in the geriatric patients with diabetes, and to GLT de-intensification in those being over-treated.


2016 ◽  
Vol 94 (7) ◽  
pp. 533-539
Author(s):  
Irina V. Gatckikh ◽  
M. M. Petrova ◽  
T. P. Shalda ◽  
E. L. Varygina ◽  
M. N. Kuznetsov ◽  
...  

The aim of thisstudy was to investigatethe efficiency ofmetabolic therapyincorrectionof cognitive impairmentin patientswith type 2 diabetes. We undertook the analysis of results of the treatment of cognitive dysfunction in 80 patients with a diagnosis of type 2 diabetes. All patients received basic hypoglycemic therapy. 32 patients (study group) received in addition to the basal glucose lowering therapy daily intravenous infusion of 10 mlcytoflavindiluted in 200 ml of a 0.9% sodium chloride solution for 10 days, followed by 2 tablets b.i.d. for 25 days.The group of comparison consisted of 29 patients given in addition to the basal glucose-lowering therapy daily intravenous infusion of 24 ml (600 mg) thioctacid diluted in 200 mL of a 0.9% sodium chloride solution for 10 days. Thereafter, they received 1 tablet ofthioctacid BV once dailyfor 30 days. The control group consisted of 19 patients who received basic hypoglycemic therapy without additional metabolic therapy.Inclusion of cytoflavin in the combined treatment ofpatients with type 2 diabetes ensured a more effective correction of cognitive impairment. There was a statistically significant improvement in optical-spatial activities (p = 0.001), attention (p = 0.001), abstract thinking (p = 0.046), and memory (p<0.001) compared to those in other groups, according to the MOS test. Positive dynamics was expressed as the improvement of the optical-spatial activities by 9,8 ± 10,3%, attention by 13,5 ± 11,8%, abstract thinking by 7,0 ± 8,9%, and memory by 23.0 ± 14 6%. The study of variations of the serum level of brain neurotrophic factor (BDNF) over time during the treatment with metabolic preparations revealedits statistically significant increase (p = 0.002) in the patients treated with cytoflavincompared with comparison (p = 0.139) and control (p = 0.078) groups. These results suggest the influence of cytoflavinon the processes of neuroplasticity under conditions of hyperglycemia, improvement of cerebral microcirculation and cerebroprotective action of this medication.


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