Frontiers in Clinical Drug Research-Diabetes and Obesity

Volume: 4

Sodium–Glucose Co-Transporters Inhibitors for Type 2 Diabetes Mellitus: The ‘New Kids on the Block’ in the Era of Evidence-based Medicine

Author(s): Cheow Peng Ooi, Norlaila Mustafa, Nor Azmi Kamaruddin and Munn Sann Lye

Pp: 58-107 (50)

DOI: 10.2174/9781681084459119040005

* (Excluding Mailing and Handling)

Abstract

Type 2 diabetes mellitus (T2DM) is a global crisis. Asia has a young, economically productive population at high risk of the disease. Poor blood glucose control and its associated risk factors resulting in disabling complications will have a catastrophic impact on patients with T2DM, their families, society, the healthcare system and the economy. Inhibiting sodium–glucose co-transporters (SGLT1/SGLT2) in the gastrointestinal tract and kidneys is the latest novel therapeutic pathway in managing the disease. In addition to controlling blood glucose, SGLT inhibitors may also reduce weight and lower blood pressure. However, these drugs are so new that long-term safety data is unavailable. Currently, six SGLT2 inhibitors are available for clinical use; they are continuously monitored for long-term adverse effects by drug regulatory authorities. Although there is some data suggesting benefits favouring Asians, most of the existing evidence from randomised controlled trials (RCTs) level are not applicable to patients in Asia with T2DM. High-quality RCTs reflecting realworld practice in this region are required for evidence-based medicine (EBM) to improve clinical care and justify the significant investments their development have required. Along with the production of high-quality EBM, emerging economies in Asia have the potential to play important roles in developing and facilitating evidence from RCTs for successful clinical practice utilisation. ‘First, do not harm’ is the fundamental tenet of clinical practice. Educating consumers of EBM about the importance of critical thinking, primary data accuracy, consistency and high-quality EBM for safe clinical practice are essential.


Keywords: Anti-hyperglycemic agents, Anti-diabetic agents, Cardiovascular outcomes, Clinical trials, Complications, Dapagliflozin, Diabetes mellitus, Efficacy, Empagliflozin, Euglycemic diabetic ketoacidosis, Evidence-based medicine, Glucose homeostasis, Glucosuria, Glycaemic control, Glycosylated haemoglobin, Hyperglycaemia, Ipragliflozin, Luseogliflozin, Perineal hygiene, Renal function, Risk factors, Sodium–glucose co-transporters inhibitors, SGLT inhibitors, Therapeutics, Tofogliflozin, Type 2, Weight reduction.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071449 and j.to_ip >=59071449 )) and ((j.from_date <= 1740529172 and j.to_date >= 1740529172 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12848) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071449 and j.to_ip >=59071449 )) and ((j.from_date <= 1740529172 and j.to_date >= 1740529172 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12848) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071449 and j.to_ip >=59071449 )) and ((j.from_date <= 1740529172 and j.to_date >= 1740529172 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12848)
      510μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 2247 and `b`.`banner_from_date` <= 1740529172 and `b`.`banner_to_date` >= 1740529172 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2247
      • 3: 1740529172
      • 4: 1740529172
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='8eb377b7634edf2a73dfc7f2cf5f5874'
      200μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    27Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        4uJxc3vF1jjOtXrw0xx0U0VwIppyR571VQkwJ1Sa
        uc_cart_id
        8eb377b7634edf2a73dfc7f2cf5f5874
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12848" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12848
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InJobktSUnlNZkhLaVM4YmxmWEExTkE9PSIsInZhbHVlIjoiT2M4VFdGRVR0OUZsWHNockhJdXZIMkVoMW9OaHR5aFNrNldNTHQ5Yk5BND0iLCJtYWMiOiIwNjJkYmE0NGQxZTU0ZDE3Nzc0ODZjZTQ5ZTMxOTg2MjczZDEzZDA0M2RjYTMyMTU2OThiOWFiMjhlYTIzNzg2IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InJobktSUnlNZkhLaVM4YmxmWEExTkE9PSIsInZhbHVlIjoiT2M4VFdGRVR0OUZsWHNockhJdXZIMkVoMW9OaHR5aFNrNldNTHQ5Yk5BND0iLCJtYWMiOiIwNjJkYmE0NGQxZTU0" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 26 Feb 2025 00:19:32 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IktjT3F3ZnFLbVJKM3FIUDBYM0RGM2c9PSIsInZhbHVlIjoiN0k1eHA1eGN5UUFMWStUWGVzQ3FQZXRjaGZWQkNrOUZaeUdUSENUWGUzWXUwaHkzYk9saWI1MXlvTjVXbm5EWTRQQmkwK3lIa2xRYi9jUzd6aEk2UnhLOUJKcXdvTHI0OExzTXZoekkrUENnZXB2OHo4YzBIVDQvTEtZVFJrWDQiLCJtYWMiOiI0N2ZhY2VhZGNjMjA2Y2NkZjk3YTg4ZWVjNDgzZDdlOThjM2I3NTIzMGY2ZjM5OGUyZTczZDU2NjA4ODljNjU1IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 12:19:32 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IktjT3F3ZnFLbVJKM3FIUDBYM0RGM2c9PSIsInZhbHVlIjoiN0k1eHA1eGN5UUFMWStUWGVzQ3FQZXRjaGZWQkNrOUZaeUdUSENUWGUzWXUwaHkzYk9saWI1MXlvTjVXbm5EWTRQQmkwK" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjBZV3BIWVFXTDBPUlQ0SmpNVGJGQXc9PSIsInZhbHVlIjoicE80OEFZQ3d2TlYwYy9wNW90Ujcvbm1HRDRCbnZ3U0VmRit1ZXRFeldmd1VVRlRnZzBzRUZyRHNObURHUXZJN3Zpa3pmbzlER29Bc0FOSkhsaHJ5VDUzMjBsS1RneHhwWU44OERLNkg3QWE0WnA4dUloajAwNDNXZmtOMDQ4KysiLCJtYWMiOiI1OTU0MzY3ZGM5YjUwMzMwMDI1MGU4NGE0ZDQ0MDk1MDVlZmY3NDRmZGUxNmVkZDJkZmRjZTRkODM0YTc1NmNlIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjBZV3BIWVFXTDBPUlQ0SmpNVGJGQXc9PSIsInZhbHVlIjoicE80OEFZQ3d2TlYwYy9wNW90Ujcvbm1HRDRCbnZ3U0VmRit1ZXRFeldmd1VVRlRnZzBzRUZyRHN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IktjT3F3ZnFLbVJKM3FIUDBYM0RGM2c9PSIsInZhbHVlIjoiN0k1eHA1eGN5UUFMWStUWGVzQ3FQZXRjaGZWQkNrOUZaeUdUSENUWGUzWXUwaHkzYk9saWI1MXlvTjVXbm5EWTRQQmkwK3lIa2xRYi9jUzd6aEk2UnhLOUJKcXdvTHI0OExzTXZoekkrUENnZXB2OHo4YzBIVDQvTEtZVFJrWDQiLCJtYWMiOiI0N2ZhY2VhZGNjMjA2Y2NkZjk3YTg4ZWVjNDgzZDdlOThjM2I3NTIzMGY2ZjM5OGUyZTczZDU2NjA4ODljNjU1IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 12:19:32 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IktjT3F3ZnFLbVJKM3FIUDBYM0RGM2c9PSIsInZhbHVlIjoiN0k1eHA1eGN5UUFMWStUWGVzQ3FQZXRjaGZWQkNrOUZaeUdUSENUWGUzWXUwaHkzYk9saWI1MXlvTjVXbm5EWTRQQmkwK" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjBZV3BIWVFXTDBPUlQ0SmpNVGJGQXc9PSIsInZhbHVlIjoicE80OEFZQ3d2TlYwYy9wNW90Ujcvbm1HRDRCbnZ3U0VmRit1ZXRFeldmd1VVRlRnZzBzRUZyRHNObURHUXZJN3Zpa3pmbzlER29Bc0FOSkhsaHJ5VDUzMjBsS1RneHhwWU44OERLNkg3QWE0WnA4dUloajAwNDNXZmtOMDQ4KysiLCJtYWMiOiI1OTU0MzY3ZGM5YjUwMzMwMDI1MGU4NGE0ZDQ0MDk1MDVlZmY3NDRmZGUxNmVkZDJkZmRjZTRkODM0YTc1NmNlIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjBZV3BIWVFXTDBPUlQ0SmpNVGJGQXc9PSIsInZhbHVlIjoicE80OEFZQ3d2TlYwYy9wNW90Ujcvbm1HRDRCbnZ3U0VmRit1ZXRFeldmd1VVRlRnZzBzRUZyRHN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "4uJxc3vF1jjOtXrw0xx0U0VwIppyR571VQkwJ1Sa" "uc_cart_id" => "8eb377b7634edf2a73dfc7f2cf5f5874" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12848" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-26 00:19:32GET/chapter/128481121929