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  • 1
    In: Diabetes Care, American Diabetes Association, Vol. 44, No. 5 ( 2021-05-01), p. 1219-1227
    Abstract: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P & lt; 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
    detail.hit.zdb_id: 1490520-6
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: The aim of this analysis of the XENSOR study was to assess the effect of 2 weight-loss drugs on hepatic serum biomarkers in patients with overweight or obesity and insufficient weight loss (WL) after a lifestyle modification program. A retrospective real-world study (RWS) was conducted comparing the effect of orlistat 120 mg tid and liraglutide (up to 3 mg daily) on liver enzymes in adult patients with BMI & gt; 30 kg/m² (or & gt; 27 kg/m² with at least a weight-related comorbidity) . The primary endpoint was to assess in a multivariate model the differences in ALT and GGT reductions between both drugs over a median follow-up period of 7 months. A secondary endpoint was to study the impact of the amount of WL on both liver enzymes. 400 patients in the group of orlistat (BMI 41.4 kg/m2, ALT 30.1 U/L, GGT 35.7 U/L) , and 100 in the group of liraglutide (BMI 39.7 kg/m2, ALT 27.3 U/L, GGT 29.1 U/L) , were included. WL with liraglutide (−7.7 kg) was significantly greater in comparison with orlistat (−3.3 kg) , p & lt;0.0001. Treatment with both drugs significantly reduced ALT (orlistat −3.8 U/L; liraglutide −5.7 U/L, both p & lt;0.05) . ALT reduction was significantly higher with liraglutide vs. orlistat (adjusted mean difference −3.4 U/L (95% CI −6.5 to −0.2 U/L) . A significant decrease in GGT levels was observed with liraglutide (−5.8 U/L, p & lt;0.0001) , but not with orlistat. Adjusted mean differences in GGT changes between both drugs were not statistically significant. 46% of patients with high ALT levels lowered this enzyme into the normal range at the end of the follow-up, without significant differences between both drugs. When patients were split into 3 groups according to their WL ( & lt;5%, 5-10% and & gt;10%) , ALT and GGT reductions were significantly higher in patients with WL & gt;10%. In summary, in this RWS ALT reductions were significantly greater with liraglutide in comparison with orlistat. The effects of both drugs on ALT and GGT were higher in those patients with clinically relevant WL ( & gt;10%) . Disclosure J.J.Gorgojo-martinez: Consultant; Mundipharma, Research Support; Novo Nordisk, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk. P.L.Lois chicharro: None. P.J.Ferreira-ocampo: None. S.C.Doejo-marciales: None. S.F.Barra-malig: None. F.Almodovar-ruiz: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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