Metformin與降低神經退化性疾病風險有關


  【24drs.com】新研究認為,Metformin對於阿茲海默氏症與巴金森氏症等神經退化性疾病可能有長期的保護效果。
  
  這篇回溯性縱向研究的資料來自Veterans' Affairs的電子病歷,路易西安那州紐奧良杜蘭大學博士候選人Qian Shi在6月11日於美國糖尿病協會(ADA)2016年科學研討會發表研究結果。
  
  Shi小姐表示,對於使用metformin超過2年者,我們發現神經退化性疾病顯著減少;Metformin可能有神經保護性。
  
  研究者校正腎功能、慢性腎臟病與其他糖尿病藥物之後,研究結果依舊成立。她指出,機轉還不清楚,但是,已知metformin可以通過血腦障蔽。
  
  會議主持人、喬治亞州亞特蘭大Emory大學醫學院醫學教授Lawrence S Phillips醫師受邀發表評論時表示,Metformin有多效性,基於多種原因而令人有極大興趣。
  
  他指出,在日前的ADA會議中,有一整個座談會探討有關metformin的新研究結果,包括它在癌症與心臟病的可能預防作用。
  
  但是,Phillips醫師同時也提出提醒,雖然研究者控制了腎功能與其他可能的干擾因素,所有流行病學分析中最難回答的問題,是根據適應症排除干擾因素。不論患者沒有使用或者一直使用metformin,可能在分析所用的估計腎絲球過濾速率(eGFR)之外的其他檢測方式是更嚴重的,我認為這在管理資料庫的流行病學分析是難以分辨的。
  
  儘管如此,他表示,這絕對值得進一步研究。
  
  Shi小姐表示,之前有關metformin和退化性疾病的資料互有矛盾,有兩篇人口研究顯示,長期使用metformin治療可以降低認知衰退風險,其他資料指出,服用metformin之患者的認知表現可能惡化,可能是因為缺乏維他命B12。另一篇試驗中,長期使用該藥與阿茲海默氏症的風險略為增加有關。
  
  目前這篇研究納入Veterans' Affairs電子病歷的50歲以上、接受胰島素治療之第二型糖尿病患者的資料,從診斷當時追蹤到死亡或研究結束。
  
  符合條件的150,435人中,41,696因為神經病變、缺乏維他命B12、之前的神經退化性疾病、認知缺損、腦血管疾病的後續影響、癌症、末期腎病等干擾因素而排除;使用胰島素的時間小於三分之二研究期間的患者也被排除。
  
  最後的研究樣本共有6,046名患者(90%以上是男性),平均年齡63歲,追蹤期中位數為5.25年。
  
  除了腎功能與其他糖尿病藥物,Shi小姐等人也控制了年齡、性別、種族、抽菸、肥胖、其他併發症病史、研究開始時的共病症。
  
  在追蹤期間,有334例診斷為失智症,其中100例為巴金森氏症、71例為阿茲海默氏症、19例為認知缺損。
  
  發生一種或一種以上神經退化性疾病的校正發生率為,未曾使用metformin者為2.08/100人-年,使用metformin不到1年者為2.47/100人-年,不到2年者為1.61/100人-年,2-4年者為1.30/100人-年,4年以上者為0.49 /100人-年。
  
  Metformin和神經退化性疾病之間的保護效果,只有在2年後才有統計上的顯著意義。
  
  相較於未曾使用metformin者,使用metformin 2-4年者之所有神經退化性疾病的風險比為0.623,使用4年以上者為0.216。
  
  失智症的結果也很顯著(2-4年為0.567,4年以上為0.252),巴金森氏症和阿茲海默氏症只有4年以上者有顯著意義(分別是0.038和0.229)。
  
  Shi小姐解釋,在失智症和巴金森氏症有類似的風險降低結果,但是其他亞型急病則無,可能是因為案例數有限。
  
  她結論指出,需要大型前瞻世代研究來確認,使用metformin和神經退化性疾病風險之間的這個關係與因果。
  
  資料來源:http://www.24drs.com/
  
  Native link:Metformin Linked to Lower Neurodegenerative Disease Risk

Metformin Linked to Lower Neurodegenerative Disease Risk

By Miriam E Tucker
Medscape Medical News

NEW ORLEANS — Metformin may exert a long-term protective effect against neurodegenerative diseases including Alzheimer's and Parkinson's, new research suggests.

Findings from a retrospective longitudinal study of data from Veterans' Affairs electronic medical records were presented June 11 here at the annual American Diabetes Association (ADA) 2016 Scientific Sessions by Qian Shi, a PhD candidate at Tulane University, New Orleans, Louisiana.

"For metformin exposure longer than 2 years, we found a significant reduction in neurodegenerative disease.…Metformin may be neuroprotective," Ms Shi told Medscape Medical News.

The results were consistent even after researchers controlled for kidney function, chronic renal disease, and other diabetes medications.

The mechanism is unclear, but metformin is known to cross the blood-brain barrier, she noted.

Asked to comment, session moderator Lawrence S Phillips, MD, professor of medicine at Emory University School of Medicine, Atlanta, Georgia, said: "Metformin has pleiotropic effects, and it is of great interest for a variety of reasons."

He added that there was an entire symposium here yesterday at the ADA meeting devoted to emerging findings regarding metformin, including its possible preventive roles in cancer and heart disease.

But at the same time, Dr Phillips cautioned that even though the investigators controlled for renal function and other potential confounders, "the hard question in all of these epidemiologic analyses is ruling out confounding by indication.…You wonder if the patients who didn't get metformin or stay on it were somehow sicker in ways other than what [estimated glomerular filtration rate] eGFR might have been picked up in the analysis. I think that's very hard to tell in an epidemiologic analysis of an administrative database."

Nonetheless, he told Medscape Medical News, "It absolutely deserves further study."

Effect Seen After 2 Years

Ms Shi said that prior data on metformin and neurodegenerative diseases have been conflicting. While two previous population studies have shown that long-term treatment with metformin may reduce the risk of cognitive decline, other data indicated that cognitive performance was worse among patients taking metformin, possibly due to vitamin B12 deficiency. And long-term use of the drug was associated with a slightly increased risk for Alzheimer's disease in another trial.

The current study population consisted of patients with type 2 diabetes older than 50 years from the Veterans Affairs electronic medical records database who were receiving insulin treatment. They were followed from the time of diagnosis until death or outcome.

Out of 150,435 who met those criteria, 41,696 were excluded for a variety of confounders, including neuropathy, vitamin B12 deficiency, prior neurodegenerative diseases, cognitive impairment, or late effects of cerebrovascular disease, cancer, or end-stage renal disease. Patients who took insulin for less than two-thirds of the study period were also excluded.

The final study sample was 6046 patients (over 90% male) with a mean age of 63 years. They were followed for a median of 5.25 years.

In addition to renal function and other diabetes medications, Ms Shi and colleagues also controlled for age, gender, race, tobacco use, obesity, and history of other complications and comorbidities at baseline.

During follow-up, 334 cases of dementia were diagnosed, as were 100 of Parkinson's, 71 Alzheimer's disease cases, and 19 with cognitive impairment.

The adjusted incidence of developing one or more neurodegenerative diseases per 100 person-years was 2.08 for those who never used metformin, 2.47 for those using metformin less than 1 year, 1.61 for less than 2 years, 1.30 for 2 to 4 years, and 0.49 for 4 or more years.

The protective relationship between metformin and neurodegenerative disease was statistically significant only after 2 years.

Compared with no metformin, the hazard ratios for 2 to 4 years of metformin therapy for all neurodegenerative diseases combined was 0.623 and for 4 or more years 0.216.

The findings were also significant for dementia specifically (0.567 at 2–4 years and 0.252 for 4+ years) and for Parkinson's and Alzheimer's diseases only beyond 4 years (0.038 and 0.229, respectively).

"Similar risk reductions occurred in dementia and Parkinson's but were not duplicated to other subtype diseases, most likely due to the limited numbers of events," Ms. Shi explained.

"A large-scale prospective cohort study may be needed to confirm the relationship and the causality between metformin exposure and the risk for neurodegenerative disease," she concluded.

Dr Shi has no relevant financial relationships. Dr Phillips has served on scientific advisory boards for Boehringer Ingelheim and Janssen and has or had research support from Merck, Amylin, Eli Lilly, Novo Nordisk, Sanofi, PhaseBio, Roche, Abbvie, Vascular Pharmaceuticals, and the Cystic Fibrosis Foundation.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

American Diabetes Association 2016 Scientific Sessions; June 11, 2016; New Orleans, Louisiana.

    
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