glucagon - like peptide 1 receptor agonists ( glp1ras ) have become an accepted part of the diabetes pharmaco - therapeutic landscape .
the glp1ras are included in guidelines from various professional bodies such as the international diabetes federation ( idf ) , the american diabetes association ( ada ) , european association for study of diabetes ( easd ) , and american association of clinical endocrinologists ( aace ) .
glp1ras can be used as second - line and third - line agents , in combination with metformin and insulin .
there is also evidence to suggest that glp1ras should be used earlier on in the natural history of diabetes , so as to utilize their full potential .
an increasing number of glp1ras are available for use , or are in advanced phases of development .
while they have earlier been divided according to chemical structure , glp1ras can also be classified based on their duration of action ( table  1 ) .
this approach makes it easier to compare and contrast the various pharmacokinetic and pharmacodynamic properties of these drugs .
short - acting glp1ras are those with a half - life of < 12  h , which requires daily or twice daily administration [ 2 , 3 ] .
intermediate - acting glp1ras are those with a half - life of > 12  h , which allow once daily injection .
long - acting glp1ras have half - lives of > 24  h [ 5 , 6 ] and can be injected as once - weekly doses .
the once - daily glp1ra , viz , liraglutide and lixisenatide , are also being developed as fixed ratio co - formulations with basal insulins , viz , degludec and glargine , respectively.table  1glucagon - like peptide 1 receptor agonists ( glp1ra)short acting  twice - daily dosage  exenatide  once - daily dosage  lixisenatideintermediate acting ( once - daily dosage )  liraglutidelong acting ( once - weekly dosage )  exenatide lar  albiglutide  semaglutidefixed ratio combinations  liraglutide  +  degludec  lixisenatide  +  glargine glucagon - like peptide 1 receptor agonists ( glp1ra )
various glp1ras have been utilizing differing strategies to prolong or protract their duration of action .
the shortest - acting glp1ra , viz exenatide and lixisenatide [ 3 , 7 ] , achieve this by exchanging amino acids at the n2 and n3 positions , thus making them resistant to breakdown by dipeptidyl peptidase 4 ( dpp4 ) .
the renal elimination of the molecule , however , continues as per physiology , and so drug levels fall to baseline prior to the next injection .
the short half - life of 24  h means that peak concentrations are maintained for just 6  h. liraglutide achieves a longer half - life ( 1213  h ) and duration of action , by having a fatty acid side chain .
this increases its size and slows down release of the glp 1 moiety from plasma albumin , thus prolonging its action .
albiglutide uses a similar albumin - binding based approach , but binds in a covalent manner to the protein . the long half - life of the albumin
 glp1 conjugate allows for a long duration of action and once - weekly administration [ 5 , 9 ] .
it conjugates glp-1 with the fc fragment of igg and thus achieves a longer duration of action [ 10 , 11 ] .
exenatide long - acting release ( lar ) is a chemical modification of exenatide , which is coupled to microspheres that allow slow and steady release of the molecule from its subcutaneous site .
in essence , a patient - centered approach implies crafting of a management strategy which involves the patient and is respectful of his or her opinion .
viewed through a larger prism , patient - centered care assumes acceptance of the bio - psychosocial model of disease .
it is understood that biomedical , psychological , and social factors impact not only the presentation of diabetes , but also its management .
apart from biological characteristics , psychosocial reality should be taken into consideration while planning a therapeutic regime .
the varieties of glp1ras available today and their unique pharmacological properties allow a patient - centered choice to be made in this class of drugs .
various factors which influence the choice of a glp1ra can be categorized according to the bio - psychosocial model ( table  2).table  2comparison of glp1rashort - acting glp1raintermediate- and long - acting glp1racontrol of fasting glycemiasuitablemore suitablecontrol of postprandial glycemiamore suitablesuitablecontrol of hba1ceffectiveeffectivefrequency of dosagedaily / twice dailyweekly / once dailycombination with basal insulincomplementary effectcomplementary effect for liraglutidecombination with premixed insulinmay show beneficial effectmay show complementary effectuse as directly observed therapy ( dot)not feasiblefeasiblegauge of needlethin ( 31 g , 32g)thick ( 23 g ) for exenatide larinjection techniquesimplerequires manual dexterity for exenatide lar , injection technique is also simple for liraglutide , titrated with the same peninjection site reactionsrarecommon , seldom with liraglutidegastrointestinal symptomsmore commonless commonincrease in pulse rateless commonmore commonweight losseffectiveeffectiveimprovement in lipid profileminimalminimalantibody formationrelatively high with exenatiderelatively high with exenatide lar ; low for liraglutideability to stop in case of adverse eventsretainedlost for once - weekly injections 
 glp1ra glucagon - like peptide 1 receptor agonists , lar long - acting release 
 glp1ra glucagon - like peptide 1 receptor agonists , lar long - acting release
the biomedical factors which inform the appropriate choice of glp1ra include efficacy , safety , tolerability , and versatility in combination with insulin .
the shorter - acting glp1ras have a greater effect on postprandial glycemia , while the longer - acting molecules lower fasting glucose to a greater extent .
short - acting glp1ras delay gastric emptying , decrease the rate of glucose delivery to the duodenum , blunt postprandial glycemia excursions , and reduce insulin levels as well .
however , their short duration of action means that optimal glucose control may not be achieved over the full 24  h .
exenatide lowers breakfast and post - dinner glucose levels to a much greater degree than post - lunch excursions .
this is expected with a twice - daily dose , keeping its pharmacokinetic profile in mind .
the hba1c reduction varies from 0.8% to 1.5% with the recommended dose of 10  g twice daily [ 1316 ] .
lixisenatide is associated with modest improvements in postprandial glucose after each meal , and in hba1c ( 0.71.0% ) , with a once - daily dose of 20  g [ 1719 ] .
this drug has a lower risk of nausea , vomiting and hypoglycemia as compared to exenatide .
the intermediate - acting liraglutide , used in a dose of 1.21.8  mg / day , improves both fasting and postprandial glucose values , leading to a 1.11.8% reduction of hba1c [ 1 , 2023 ] .
gastrointestinal effects and hypoglycemia are less common than with exenatide ; liraglutide also exhibits added benefits of low antibody formation , reduction in systolic blood pressure , and greater weight loss .
the drug is associated with a slight increase in pulse rate , and the impact of this positive chronotropic effect on cardiovascular health is uncertain .
intermediate- and long - acting glp1ras exhibit greater effect on fasting glucose levels , as they continue to act during the nighttime .
they do not have a significant effect on gastric motility , as the initial slowing is abolished due to tachyphylaxis .
the intermediate - acting and long - acting glp1ras cover all 24  h glucose control including fasting glucose .
the short - acting glp1ras probably also achieve weight loss through central effects mediated via the hypothalamus .
longer - acting drugs such as albiglutide have a lower hba1c reduction ( 0.78% vs. 0.99% ) and lower body weight reduction
( 0.62 vs. 2.21  kg ) probably because of the larger size which prevents entry into the central nervous system [ 25 , 26 ] .
the weekly dose of 30  mg , facilitated by a long half - life of 68  days , is associated with low rates of nausea and hypoglycemia , but significant local injection site reaction [ 27 , 28 ] .
dulaglutide , too , can be administered once weekly with its half - life of 90  h [ 11 , 12 ] .
significant hba1c reduction ( 1.35% ) and weight reduction ( 2.43  kg ) have been noted with doses of 1  mg once weekly for the first 4  weeks , followed by 2  mg weekly for 12  weeks .
injection site reactions such as nodule formation are most often observed with exenatide lar , which also needs thicker gauge needle for administration [ 2932 ] .
while diarrhea occurs more frequently with longer - acting compounds , nausea seems to be more common with short - acting glp1ra .
gastroparesis may be an indication to choose intermediate- or longer - acting glp1ra , while being a relative contraindication for the shorter - acting glp1ra .
the duration of action of glp-1 analogs determines the possible combination with a short - acting insulin or a basal insulin .
the short - acting exenatide can be given with a basal insulin as it has a greater effect on postprandial glucose levels because of its shorter half - life .
in contrast , the longer - acting glp-1 analogs exert greater effect on fasting glucose levels than shorter - acting glp-1 analogs .
the possible combination of a long - acting glp-1 analog with a short - acting insulin would also offer the advantages of complementary pharmacologies and could theoretically reduce both fasting and postprandial blood glucose levels .
a positive chronotropic effect has been noted with intermediate- and long - acting glp1ra , but not with the short - acting molecules .
the short - acting drugs are also associated with greater improvements in postprandial lipid excursions : these factors may encourage their use in specific patients with cardiovascular morbidity .
another biomedical factor which determines the choice of glp analog prescribed is the effect on autonomic functions .
liraglutide has less effect on gastrointestinal motility than short - acting glp-1 analogs like exenatide and lixisenatide [ 34 , 35 ] .
thus , liraglutide is a better choice in diabetic patients with impaired autonomic functions . on the other hand , exenatide and lixisenatide
thus , careful assessment of the expected efficacy ( fasting vs. postprandial vs. overall glycemic control ) , anticipated risk of side effects ( gastrointestinal symptoms , hypoglycemia , antibody formation , injection site reactions ) , effect on weight , cost and comorbid conditions ( dyslipidaemia , hypertension ) can help individualize the choice of glp1ra .
the ability of the patient to self - inject , to adhere to pre - specified times of injection(30  min before meals for exenatide ) , manual dexterity , frequency of contact with health - care providers , meal pattern followed , and adherence to therapy are some of these issues . for a person who can self - inject ,
use of exenatide lar , however , requires some amount of manual dexterity , as it has to be self - mixed prior to injection . for those unable or unwilling to self - inject and dependent upon a caregiver for the same , a once - weekly injection of long - acting glp1ra represents a useful therapeutic strategy
this once - weekly injection can be administered as directly observed therapy ( dot ) , akin to that used in tuberculosis control programs .
this approach has the added advantage of encouraging regular patient provider contact , which facilitates early detection of adverse events and complications , and encourages more efficient lifestyle modification .
it is also helpful in patients who may not adhere to more frequently administered therapy .
patients who consume heavy breakfast and dinner may benefit from exenatide twice daily , while those who take a light dinner may wish to take lixisenatide .
patients with irregular meal habit and lifestyles , which put them at risk of hypoglycemia , will respond to once - weekly drugs without major safety concerns .
the different glp-1 analogs have been compared with respect to the improvement in the quality of life and treatment satisfaction .
the increase in patients treatment satisfaction from baseline is significantly higher with 1.8  mg liraglutide than with sitagliptin , but the increase with 1.2  mg liraglutide versus sitagliptin is not significant .
no difference was perceived in the convenience of treatment between the oral versus injectable . compared to patients on traditional therapy which was insulin ,
liraglutide 1.8  mg versus glimepiride improves psychological and emotional well - being and health perceptions by reducing anxiety and worry associated with weight gain .
the preceding discussion provides a reasonably robust evidence - based assessment upon which an appropriate glp1ra can be chosen or changed .
further research and experience will help utilize glp1ra therapy in the best possible manner for the benefit of people with diabetes .
 the individualized treatment of type 2 diabetes mellitus , using various glucagon - like peptide receptor agonists ( glp1ras ) , has recently been described . as experience with existing glp1ras grows , and as newer molecules in the development pipeline continue to progress , interest related to these drugs continues to grow . 
 this article describes a person - centered approach , using the bio - psychosocial model of health , to help individualized decision making related to choice of glp1ra . 
 it utilizes an evidence - based approach to discuss various biomedical and psychosocial factors which may influence choice of glp1ra . 
Introduction
Classification
Protraction of Duration of Action
Patient-Centered Philosophy
Factors Influencing Choice of GLP1RA
Biomedical Factors
Psychosocial Factors
Conclusion