Frontiers in Clinical Drug Research-Diabetes and Obesity

Volume: 2

Advances in New Drugs for Diabetes Treatment: GLP-1 Mimetics and DPP-4 Inhibitors

Author(s): Xianglan Sun, Yao Wang and Minglong Li

Pp: 150-188 (39)

DOI: 10.2174/9781681081854116020008

* (Excluding Mailing and Handling)

Abstract

The dramatic rise in the prevalence of obesity and diabetes is associated with increased mortality, morbidity as well as public health care costs worldwide. The need for new effective and long-lasting drugs is urgent. Recent research has focused on the role of incretin in the maintenance of glucose homeostasis through their actions on both α- and β- cell function. Moreover, increased knowledge of the pathophysiology of diabetes has contributed to the development of novel drugs, including injectable glucagon-like peptide-1 (GLP-1) mimetics, and oral dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1 agonists mimic the effect of this incretin, whereas DPP-4 inhibitors prevent the inactivation of the endogenously released hormone. GLP-1 appears to be involved in both peripheral and central pathways mediating satiety. Clinical trials have shown that two GLP-1 receptor agonists exenatide and liraglutide have a weight-lowering potential in non-diabetic obese individuals. Furthermore, they may also hold a potential in preventing diabetes as compared to other weight loss agents. Both agents offer an effective alternative to the currently available hypoglycaemic drugs but further evaluation is needed to confirm their clinical roles and safety. The purpose of this review is to summarize the background of the incretin, and the roles and side effects of the GLP-1 agonists and DPP-4 inhibitors in clinical trials. In addition, up-to-date literature on GLP-1 agonists and DPP-4 inhibitors based clinical therapies will be summarized with a special mention of their weightlowering properties. In conclusion, the incretin impairment, which seems to exist in both obesity and diabetes, may link these two pathologies and underlines the potential of incretin based therapies in the prevention and treatment of obesity and diabetes.


Keywords: Alogliptin, DPP-4 Inhibitors, Exenatide, GLP-1 Agonists, Incretin, Linagliptin, Liraglutide, Saxagliptin, Sitagliptin, Vildagliptin.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
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      • 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 <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740346521 and j.to_date >= 1740346521 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 9074) 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 <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740346521 and j.to_date >= 1740346521 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 9074) 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 <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740346521 and j.to_date >= 1740346521 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 9074)
      870μsalphaeurekaselec_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` = 1977 and `b`.`banner_from_date` <= 1740346521 and `b`.`banner_to_date` >= 1740346521 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.47msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1977
      • 3: 1740346521
      • 4: 1740346521
      • 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='d895239fc1d198d8b2f7f4dcd3d430b0'
      250μsalphaeurekaselec_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
    10Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        mzRTH16QabPqAviUJgPlcYI952TdDMB7Q4t2g0Wz
        uc_cart_id
        d895239fc1d198d8b2f7f4dcd3d430b0
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/9074" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/9074
        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=eyJpdiI6ImpWbCtPMEhaYXZUc2JPUTFkb3gwd3c9PSIsInZhbHVlIjoiKzFkN3BXNi9KZlBsYUJHTHgxRngzMWM0ZHZJYW5aZ0hIZldtcXpUWG50TT0iLCJtYWMiOiJjZDAzMWEyZTM2ZTQ0ZDg3YTJiNGZmOWM4MzIzZDVmOGUxZjRlOWQ3ZTc4MmRiYmEzOTFjZjgyZjQ2NjkyNzBiIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImpWbCtPMEhaYXZUc2JPUTFkb3gwd3c9PSIsInZhbHVlIjoiKzFkN3BXNi9KZlBsYUJHTHgxRngzMWM0ZHZJYW5aZ0hIZldtcXpUWG50TT0iLCJtYWMiOiJjZDAzMWEyZTM2ZTQ0" ] "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 => "Sun, 23 Feb 2025 21:35:21 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldnaTVFM0dVRVo1cXRlM2Nwclp4THc9PSIsInZhbHVlIjoiR1VjRDBzcnoyOUwzZ1RCaUl0U3ZYc3IvRVpsa1l0VDNjdUh5SVB2WVZpRlg0WTNtQ1NQZ3UwOGp6Mm8yMGY5eDRwOG92dzRtMVNBbStvTmsxUlRnd2d4dUVJcG12MzZmMmJ6bklZTXhaKzhQdlZRVUxrbEs5V1dSOTN5UDF0R0QiLCJtYWMiOiI4ZjJjYzc2OGE2MWYwZjY3N2FmZWIyYjJiZTdjNzkwZDkzYTFiYzI1ODUzYTQzYjc1NWRmNGY3YTg5ZmI1ZDg5IiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 09:35:21 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IldnaTVFM0dVRVo1cXRlM2Nwclp4THc9PSIsInZhbHVlIjoiR1VjRDBzcnoyOUwzZ1RCaUl0U3ZYc3IvRVpsa1l0VDNjdUh5SVB2WVZpRlg0WTNtQ1NQZ3UwOGp6Mm8yMGY5eDRwOG92d" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImJ3SFphZ0FmMjhBUmFYYkNuc1UvcEE9PSIsInZhbHVlIjoiQ0txTzZxT3FhZFdnMGNHWWJvdVhOaEphY0RHMXZPazI5ZzhqWlV3Slp6UCtFWGVMQ1llU1pWdmNhMThlK2preENSM3lsM3pWVVcyeThGQXduMklQMW1WdVVVM2d5YWVSOVBKMnJKUTNQNHRkNDdkSWt0ajBjRDNkRnZYaXJuT2oiLCJtYWMiOiJiOTAzZDhhZjAyOThmODJiOGVjM2JkY2M1MTY5NjkyYWE4YmFjZTg5NDA2NjRkOGFjM2NjNjZjYzY1ODQ5YzExIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImJ3SFphZ0FmMjhBUmFYYkNuc1UvcEE9PSIsInZhbHVlIjoiQ0txTzZxT3FhZFdnMGNHWWJvdVhOaEphY0RHMXZPazI5ZzhqWlV3Slp6UCtFWGVMQ1llU1pWdmN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldnaTVFM0dVRVo1cXRlM2Nwclp4THc9PSIsInZhbHVlIjoiR1VjRDBzcnoyOUwzZ1RCaUl0U3ZYc3IvRVpsa1l0VDNjdUh5SVB2WVZpRlg0WTNtQ1NQZ3UwOGp6Mm8yMGY5eDRwOG92dzRtMVNBbStvTmsxUlRnd2d4dUVJcG12MzZmMmJ6bklZTXhaKzhQdlZRVUxrbEs5V1dSOTN5UDF0R0QiLCJtYWMiOiI4ZjJjYzc2OGE2MWYwZjY3N2FmZWIyYjJiZTdjNzkwZDkzYTFiYzI1ODUzYTQzYjc1NWRmNGY3YTg5ZmI1ZDg5IiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 09:35:21 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IldnaTVFM0dVRVo1cXRlM2Nwclp4THc9PSIsInZhbHVlIjoiR1VjRDBzcnoyOUwzZ1RCaUl0U3ZYc3IvRVpsa1l0VDNjdUh5SVB2WVZpRlg0WTNtQ1NQZ3UwOGp6Mm8yMGY5eDRwOG92d" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImJ3SFphZ0FmMjhBUmFYYkNuc1UvcEE9PSIsInZhbHVlIjoiQ0txTzZxT3FhZFdnMGNHWWJvdVhOaEphY0RHMXZPazI5ZzhqWlV3Slp6UCtFWGVMQ1llU1pWdmNhMThlK2preENSM3lsM3pWVVcyeThGQXduMklQMW1WdVVVM2d5YWVSOVBKMnJKUTNQNHRkNDdkSWt0ajBjRDNkRnZYaXJuT2oiLCJtYWMiOiJiOTAzZDhhZjAyOThmODJiOGVjM2JkY2M1MTY5NjkyYWE4YmFjZTg5NDA2NjRkOGFjM2NjNjZjYzY1ODQ5YzExIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImJ3SFphZ0FmMjhBUmFYYkNuc1UvcEE9PSIsInZhbHVlIjoiQ0txTzZxT3FhZFdnMGNHWWJvdVhOaEphY0RHMXZPazI5ZzhqWlV3Slp6UCtFWGVMQ1llU1pWdmN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "mzRTH16QabPqAviUJgPlcYI952TdDMB7Q4t2g0Wz" "uc_cart_id" => "d895239fc1d198d8b2f7f4dcd3d430b0" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/9074" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:35:21GET/chapter/90741121912