Consequence of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and Glucophage on glycemic control in patients with type 2 diabetes.
Diabetes Care. 2007 August volume 30, [ issue 8 ] pgs 1979-1987
In a 24-week, transnational randomized, double-blind, placebo-controlled, parallel-group survey, 1,091 patients with type 2 diabetes were carried out to find the consequence of the initial combination of Glucophage with sitagliptin under certain conditions. The efficaciousness of sitagliptin was measured by measuring HbA1c value, fasting plasma glucose ( FPG ) , fasting serum insulin, fasting serum proinsulin, and fasting lipoids. Change from baseline in the
proinsulin-to-insulin ratio and homeostasis
theoretical account appraisal of I?-cell map
( HOMA-I? ) – this shows the appraisal of I?-cell
map, and alteration from baseline
in HOMA of insulin opposition
( HOMA-IR ) and quantitative insulin sensitiveness cheque index, which besides estimates the insulin opposition were used in the rating of sitaglipitn.
The safety of sitagliptin was besides assessed utilizing the aggregation of informations on the different inauspicious events experienced, physical scrutinies, critical marks, EKGs and organic structure weight throughout the survey. The parametric quantities measured in both appraisals were used to accomplish the efficaciousness and safety as they are all factors in finding glycemic control every bit good as decreased inauspicious events.
This randomized cohort survey was unbiased every bit good every bit valid as the research was conducted utilizing a randomized, double-blind, placebo-controlled, parallel-group survey with 1,091 patients and all research lab values were obtained were done in reputable labs. This information was besides utile as it gave consecutive consequences in the efficaciousness parametric quantities every bit good as reduced inauspicious effects in the safety parametric quantities. The research was conclusive of the consequences because it showed that the glycemic degrees were controlled in monotherapy every bit good as multi therapy and there were minimum side effects which proved that sitagliptin is efficient and safe to utilize.
Charbonnel Bernard, Karasik Avraham, Liu Ji, Wu Mei, et Al.
Efficacy and Safety of the Dipeptidyl
Peptidase-4 Inhibitor Sitagliptin Added to
Ongoing Metformin Therapy in Patients
With Type 2 Diabetes Inadequately
Controlled With Metformin Alone.
Diabetic Care 2006 Dec 1 volume 29 ( issue12 ) pgs 2638-2643
This cohort survey provided a clinical test on the safety and efficaciousness of sitagliptin utilizing monotherapy and multiple therapies ( Glucophage and sitagliptin ) . The population tested were work forces and adult females ( aged
18-78 old ages ) with type 2 diabetes and unequal glycemic control. This survey used metformin together with sitagliptin to demo its safe in multitherapy. The measurings of HbA1c, fasting plasma glucose, 2-h station repast glucose, Fasting insulin,
fasting C-peptide, fasting proinsulin-to-insulin ratio, station repast insulin and C-peptide countries under the curve ( AUCs ) , post meal insulin AUC-to-glucose AUC ratio, homeostasis theoretical account appraisal of I?-cell map, and quantitative insulin sensitiveness cheque index were done on sitagliptin Vs placebo. These values were measured to demo the efficaciousness with the usage of sitagliptin by utilizing a attention deficit disorder on drug therapy, metformin versus placebo. The safety and tolerability were assessed throughout the survey by supervising for inauspicious
experiences, physical scrutinies,
critical marks, organic structure weight and 12-lead EKGs
( ECGs ) . This would bespeak that with minimum side effects the drug is safe to utilize.
This survey was unbiased since a transnational, randomized,
parallel-group survey was done with a placebo controlled,
period to administrate sitagliptin and placebo. It was besides valid as multiple clinical tests and articles were used to reexamine the information provided. . Consequences were favourable as sitagliptin showed minimal side effects and therefore it is safe to utilize. This survey was helpful as it demonstrated the efficaciousness and safety of sitagliptin. The article was besides conclusive of the consequences as it proved to be safe to utilize in patients utilizing Glucophage every bit good as effectual in glycemic control when compared to placebo. A restriction to this survey was the continuance of proving the HbA1c. The experiment should hold been longer than six months to obtain precise consequences since HbA1c is to be tested every three months.
Chan J. C. N. , Scott R. , Ferreira A. J. C. , etal
Safety and efficaciousness of Sitagliptin In patients with type 2 diabetes and chronic nephritic inadequacy.
Diabetess, Obesity and metamorphosis, 2008, Volume 10 ( 7 )
The cohort survey was done to find the safety and efficaciousness of sitagliptin in type 2 diabetes patients who are renally impaired at different phases for 54 hebdomads. The mark population for this survey had clinical history of type 2 diabetes and nephritic
inadequacy, a‰?18 old ages of age The factors that were measured to demo the safety were physical scrutinies, critical marks,
Electrocardiograms ( ECGs ) and marks and symptoms for any farther nephritic damage were observed. The factors that were measured to demo efficaciousness of sitagliptin were HbA1c and fasting plasma glucose. These values were measured to place the efficaciousness and safety of sitagliptin in renally impaired population where dose accommodation was required.
This survey was valid as the experiment was done for a long continuance of 54 hebdomads and set together utilizing updated reputable diaries and articles. This survey was unbiased since a placebo controlled group was used in a two-base hit blinded survey with the absence of the usage of any trade name names. This survey was helpful because it showed that sitagliptin was good tolerated and provided an effectual glycemic control in patients with type 2 diabetes and chair to severe nephritic inadequacy. The decision was besides supportive of the findings because the hyperglycemic degrees were controlled in renally impaired patients and the hypoglycaemia experienced was non every bit terrible as compared to the placebo group. dose-adjusted sitagliptin was good tolerated
and provided effectual glucose take downing in patients with type 2 diabetes and chair to severe nephritic inadequacy, including those on dialysis, in this 54-week survey.
Even though this survey was valid it had restrictions where the serum creatinine clearance and creatinine clearance degree were non tested after the disposal of sitagliptin after the survey. Serum creatinine clearance and creatinine clearance should be tested to find nephritic inadequacy after the usage of sitagliptin to find if it further worsened the kidney or non.
Hermansen K, Kipnes M Luo, E Fanurik D, Khatami H, Stein P.
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride entirely or on glimepiride and Glucophage.
Diabetess, Obesity & A ; Metabolism ; Sep2007, Vol. 9 Issue 5, p733-745.
This cohort survey was based on the efficaciousness and safety of sitagliptin in type 2 diabetic patients who are inadequately controlled by glimepiride entirely or glimepiride and Glucophage in a 24 hebdomad survey. The population chosen were merely both Men and adult females, a‰?18 and a‰¤75 old ages of age, with type 2
Diabetess. These patients were either on glimepiride or metformin intervention or both. The parametric quantities measured were HbA1c, fasting plasma glucose and 2 hr station repast glucose. These parametric quantities were measured to find the efficaciousness of sitaglitin in monotherapy every bit good as multitherapy. Safety parametric quantities assessed included inauspicious events, research lab safety analytes, bodyweight, critical marks and ECGs. Inferential testing was performed on the between-group differences for hypoglycaemia, selected GI inauspicious effects and alteration in organic structure weight. An ANCOVA theoretical account was besides utilised to measure the consistence of the HbA1c-lowering consequence of sitagliptin relation to placebo across pre-defined subgroups.
This survey was unbiased because the method used to carry on this experiment was a transnational, randomized, double-blind, and parallel-group survey with a single-blind placebo run-in period followed by a double-blind placebo-controlled intervention period. This survey was most valid because the observations made on safety with sitagliptin versus placebo had a assurance interval ( CI ) of 95 % which shows great dependability. This cohort survey was utile as it gave relevant information on the hunt carried out. It showed a decrease in the HbA1c, fasting plasma glucose and 2 hr station repast glucose thereby commanding hyperglycemic degrees in type 2 diabetes patients demoing its efficaciousness. Sitagliptin in combination with other drugs were by and large good tolerated. No meaningful differences
were observed between the two groups in the incidence
of serious inauspicious events that can take to a discontinuance of therapy. The survey showed that a diffident addition in weight, consistent with the achieved grade of glycaemic betterment. The higher incidence of hypoglycaemia was due to the interactive consequence of the glimepiride and Glucophage.
What clinical grounds is at that place on efficaciousness and safety of sitagliptin?
Before these articles were chosen it was carefully scrutinized and analysed to obtain valid and most up to day of the month information as the safety and efficaciousness is the first precedence of the patient. Based on research of the legion clinical tests, sitagliptin is safe and effectual to utilize in patients who are 18 old ages and over in monotherapy every bit good as multi therapy. Sitagliptin is safe to utilize as it produces minimum side effects and no serious inauspicious events. The inauspicious effects noted were nasopharyngitis, Urinary piece of land infection, arthralgia, back hurting, and cough where the differences were by and large little. Sitagliptin is undistinguished to burden addition, safe in nephritic inadequacy but the dosage must be adjusted and does non do inordinate hypoglycaemia. No bosom failure was seen in sitagliptin. Sitagliptin is besides safe to utilize in multi therapy based on clinical tests. Sitagliptin used with other antidiabetic drugs like Glucophage, Glucotrol and glimepiride can increase the hazard for hypoglycemia and can frequently ensue in weight addition so patient ‘s blood glucose degree demands to supervise every bit good as diet ansd exercising is mainstay for non-pharmacotherapy intervention. Sitagliptin and Glucophage besides displayed little GI inauspicious effects.
Sitagliptin was seen to be really effectual since it reduced the HbA1c degree to a significant extent from clinical grounds and was comparatively stable and the 24th hebdomad from all the surveies conducted. The blood glucose degree was besides decreased by a important amount- fasting plasma blood glucose and 2 hr station repast plasma glucose. Sitagliptin besides proved to increase I?-cell map together with proinsulin-to-insulin ratio was significantly improved. When health care professionals are ordering or distributing this drug they should be good cognizant of the inauspicious events it can do when used in monotherapy or multitherapy in patients who might be affected. Patient guidance is really of import in supervising these parametric quantities.
Contraindications of Sitagliptin
Writers, Title, Text/ Journal Information
Summary of Findingss
Larcy F Charles, Armstrong Lora L ; Goldman P Morton, Lance L Leonard, et Al
Drug Information Handbook
Published by Lexi-Comp ‘s Management System, 2009
Sitagliptin, page 1375-1376
The contraindications of sitagliptin were clearly stated in this enchiridion which is normally used by individuals in the medical field. The contraindications stated are as follows:
Serious hypersensitivity- this can be seen as anaphylaxis and atrophedema
Hypersensitivity to any constituent in the preparation
Type 1 diabetes mellitus ( insulin dependant diabetes mellitus- IDDM )
Diabetic diabetic acidosis
This information was valid and indifferent because non merely did they use the merchandise literature but it was based on many clinical tests and reviewed articles by wellness attention professionals and other dedicated writers. This information was utile because the contraindications found were based on clinical tests, it was current and accurate.
Martin John, Jordan Bryony, Macfarlane Colin, Ryan Rachel, Wagle Shama, Homar Heidi et Al
British National Formulary
Volume 55, March 2008 Chapter 6 page 371 hormone system
The information sourced provided contraindications of sitagliptin in a concise signifier.
The contraindications documented under sitagliptin were:
Keto-acidosis which is normally seen in type 1 diabetes
gestation ( avoid sitagliptin in gestation because of toxicity in carnal surveies. for this ground insulin is usually substituted in gestation in all diabetics unless otherwise contraindicated )
breastfeeding ( Avoid sitagliptin in breastfeeding because it is present in milk when conducted in animate being surveies
This information was valid and indifferent because along with the merchandise literature, authorative information was used and information in the British National Formulary is updated twice a twelvemonth. The information was helpful as it gave the needed information on the contra indicants that were grounds based.
Are there any patients for whom sitagliptin is contraindicated?
The beginnings used to obtain information on contra indicants were FDA approved. Even though sitagliptin is safe to utilize it may do decease or life baleful effects. Sitagliptin is contraindicated in a little population. It is documented based on clinical tests that sitagliptin is contraindicated in type 1 diabetes and later patients with diabetic acidosis. Evidence has shown that sitagliptin can hold serious hypersensitivity reactions doing – anaphylaxis and atrophedema every bit good as hypersensitivity to any constituent in the preparation. Sitagliptin can come in breast milk so it should be avoided in breastfeeding female parents where surveies were conducted in animate beings. Sitagliptin is besides contraindicated in gestation based on clinical surveies in animate beings nevertheless it can be classified as Class B ( Animal surveies have revealed no grounds of injury to the foetus, nevertheless, there are no equal and well-controlled surveies in pregnant adult females.
Animal surveies have shown an inauspicious consequence, but equal and well-controlled surveies in pregnant adult females have failed to show a hazard to the foetus in any trimester. ) .
Before ordering or urging this drug, physicians and other health care professionals should take a thorough patient history to avoid human deaths in the disposal of sitagliptin. HealthCare professionals should besides warn patients if they observe any alterations to describe to them instantly. This drug MUST be avoided in the state of affairss mentioned.
Dosing and disposal
Writers, Title, Text/ Journal Information
Summary of Findingss
Larcy Charles F, Armstrong Lora L ; Goldman Morton P, Lance Leonard L, et Al
Drug Information Handbook
Published by Lexi-Comp ‘s Management System, 2009
Sitagliptin, page 1375-1376
The information obtained is different paths of disposal with regard to their doses.
Oral path of disposal:
For diabetes type 2: Adults – take 100mg one time day-to-day
If sitagliptin is being used concomitantly with a sulfonylurea, a dose accommodation is required. Subsequently the dosage needs to be reduced.
Table 1 demoing Dosage accommodation for renally impaired patients.
Creatinin clearance mL/min
No dose accommodation is required.
a‰?30 to & lt ; 50
( serum creatinin in males: & gt ; 1.7 to a‰¤3.0 mg/dL and females: & gt ; 1.5 to a‰¤2.5mg/dL )
50mg one time day-to-day
& lt ; 30
( serum creatinin in males: & gt ; 3.0mg/dL and females: & gt ; 2.5mg/dL )
25mg one time day-to-day
End Stage Renal Disease necessitating haemodialysis or peritoneal dialysis
25mg one time day-to-day. Administered without respects to timing of haemodialysis.
Dose accommodation in hepatic Damage:
Mild to chair ( Child-Pugh mark 7-9 ) : No accommodation is required
Severe damage ( Child-Pugh mark & gt ; 9 ) – surveies have non been conducted.
Sitagliptin can be taken with OR without respects to repasts.
The information provided by the Drug Information Handbook was valid and indifferent because non merely did the merchandise literature was used but it was based on many clinical tests, reviewed articles and other important reappraisals. The information provided was utile as it gave the dose and disposal in a clear and concise signifier for different cases.
Cada Denis J, Levien Terri,
Baker Danial E,
Hospital Pharmacy, Formulary Drug Reviews 2007, 42 ( 2 ) , page 133-140
This information provides the doses along with waies of disposal of sitagliptin phosphate.
The recommended dosage of sitagliptin is 100mg one time day-to-day given either as a monotherapy or combination therapy with Glucophage or a peroxisome
Sitagliptin can be taken with or without repasts.
Table 2 demoing Dosage accommodation for renally impaired patients.
Creatinin clearance [ mL/min ] / serum creatinine [ mg/dL ]
a‰?50 OR SrCra‰¤1.7 in work forces OR a‰¤1.5
in adult females
No dose accommodation is necessary.
moderate nephritic damage –
30 to 50
SrCr. in males: 1.7 to 3.0 mg/dL and females: 1.5 to 2.5mg/dL )
Dose needs to be altered to 50mg one time day-to-day.
Patients with terrible nephritic damage with CrCl & lt ; 30 OR
( SrCr in males & gt ; 3.0mg/dL and females & gt ; 2.5mg/dL )
Dose is altered to 25mg one time day-to-day
End Stage Renal Disease necessitating haemodialysis or peritoneal dialysis
The dosage is altered to 25mg one time day-to-day as good. Sitagliptin is administered without respects to timing of haemodialysis.
The survey was valid and indifferent since it was assessed on the footing of reappraisals by many articles such as diary of clinical pharmacological medicine, diabetes diary, and clinical pharmacological medicine therapeutics journal etc. These diaries provided up to day of the month and accurate findings. The information was utile since the dose agenda was given for each category of renally impaired persons that were supported by lab consequences for both creatinine and serum clearance.
NPS Rational Assessment of Drugs and Research
Sitagliptin ( JANUVIA ) for type two diabetes: Dosing Issues.
This research shows the proper dosing and disposal of sitagliptin in combined therapy, monotherapy every bit good as in renally impaired patients.
The recommended dosage of sitagliptin is 100mg day-to-day with OR without respects to repasts.
Table 3 demoing dosing accommodations for different state of affairss.
Sitagliptin combined with sulfonylurea
patients with a creatinine clearance of 30 to & lt ; 50 mL/min
Dose of 50mg one time day-to-day is required.
patients with end phase nephritic failure whom requires hemodialysis or a creatinine
clearance & lt ; 30 mL/min
Dose should be altered to 25mg one time day-to-day.
The information obtained is valid since the website site complies with HONcode ‘s criterion for trusty wellness information.
The information presented in this stuff was derived from a critical analysis of a broad scope of important grounds. The information stated in the article was supported by the decisions made in these randomized controlled tests. This rating was non biased because the web site was non sponsored by the trade name drug, but it was funded by the Australian Government Department of Health and Ageing. One of the restrictions to this article
What are the recommended paths of disposal and subsequent dosing?
Sitagliptin can merely be taken orally based on clinical tests with or without respects to repasts. From experiments conducted merely grownups who are 18 old ages and older can take sitagliptin. From informations collected sitagliptin is taken 100mg one time day-to-day. This dosage, nevertheless, is altered in the presence of nephritic complications. The dosage must be adjusted for patients at different phases of nephritic failure like mild, moderate or terrible nephritic failure and terminal phase nephritic failure. Healthcare professionals need to take a thorough patient history and order lab trials for serum and creatinine clearance to find if dose accommodation is necessary for the several patients. The dose accommodation is due to the elimination of sitagliptin being extensively renal.
In some instances dose can be adjusted in patients who are taking sulfonylureas concomitantly with sitagliptin since they can hold a higher hazard of hypoglycaemic effects. Taking these two drugs can besides increase hazard of weight addition. Health professionals should rede patients of sudating, shudders and giddiness if hypoglycaemia occurs. Healthcare professionals should besides rede that exercising and diet is the pillar of direction of diabetes mellitus.
Goldstein J Barry, Feinglos N Mark, Lunceford K Jared, Johnson Jeremy, Williams-Herman E Debora. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and Glucophage on glycemic control in patients with type 2 diabetes. Diabetes Care 2007 August volume 30 ( 8 ) :1979-1987. In Academic Research Library [ database on the cyberspace ] [ cited 2010 March 10th ]
Charbonnel Bernard, Karasik Avraham, Liu Ji, Meininger Gary. Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone. Diabetic Care 2006 Dec 1 ; 29 ( 12 ) :2638-2643. In Academic Research Library [ database on the cyberspace ] [ cited 2010 March 10th ] . Available from hypertext transfer protocol: //www.proquest.com/ ; Document I.D. 1184538331.
Chan J. C. N. , Scott R. , Ferreira A. J. C. , Sheng D. , Gonzalez E. , Davies M. J. , Stein P. P. , Kaufman K. D. , Amatruda J. M. , Williams-Herman D. Safety and efficaciousness of sitagliptin in patients with type 2 diabetes and chronic nephritic inadequacy. Diabetes, fleshiness and metamorphosis [ Serial on the cyberspace ] ( 2008, July ) , [ cited March 4, 2010 ] ; 10 ( 7 ) : 545-555. Available from: Academic Search Complete.
Hermansen K, Kipnes M, Luo E, Fanurik, D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride entirely or on glimepiride and Glucophage. Diabetes, Obesity & A ; Metabolism ; Sep2007, 9 ( 5 ) : 733-745.
Larcy Charles F, Armstrong Lora L, Goldman Morton P, Lance Leonard L. Drug Information Handbook: United States: Lexi-Comp ‘s Management System ; 2009, 1375-1376.
Martin John, Jordan Bryony, Macfarlane Colin, Ryan Rachel, Wagle Shama, Homar Heidi et Al. British National Formulary Volume 55 March 2008. London, U.K: BMJ Group and RPS Publishing ; 2008
Larcy F Charles, Armstrong L Lora, Goldman P Morton, Lance L Leonard. Drug Information Handbook: United States: Lexi-Comp ‘s Management System ; 2009, 1375-1376
Dennis J. Cada, Terri Levien, Danial E. Baker. Sitagliptin Phosphate. Formulary Drug Reviews [ consecutive online ] 2007 Feb [ cited 2010 Mar 10 ] ; 42 ( 2 ) :133-140. Available from: Uniform resource locator: hypertext transfer protocol: //www.factsandcomparisons.com/assets/hpdatenamed/20070201_feb2007_form.pdf
NPS Rational Assessment of Drugs and Research [ Online ] . 2008 August [ cited 2010 March 8 ] ; Available from: Uniform resource locator: hypertext transfer protocol: //www.nps.org.au/__data/assets/pdf_file/0010/59968/Sitagliptin_Januvia_for_type_2_diabetes_mellitus_-_RADAR_Aug_08_To_print.pdf