Analysis of the management and therapeutic performance of diabetes mellitus employing special target

Table 1 Anti-diabetes medications authorized by the Food and Drug Administration

Type of agents	Dosing	Formulation	FDA clearance date	Observations
Euglycemics: Drugs that lower blood sugar levels to typical levels. These drugs shouldn’t result in glucose
Biguanides: Reduces intestinal glucose absorption and hepatic glucose release and enhances insulin sensitivity (increases glucose uptake and utilization)
Metformin: Glumetza Fortamet®, Glucophage XR®, Glucophage®	500 mg, 1000 mg. 500 mg, 750 mg pills. 500 mg, 750 mg pills. 500 mg, 850 mg, and 1000 mg pills	Initial dose: 500 mg once daily. Dose: 2-3 times a day. Range: 500-2550 mg. Initial: 500 mg 2 times daily or 850 mg once a day	December 1994	SE: Can’t use it if you have problems with your liver or kidneys, take medicine for heart failure, or drink too much alcohol. Consume with food (ER with evening meal) 0.03 cases per 1000 individuals are lactic acidosis. Gastrointestinal complaints (3%) such as diarrhea, nausea, and upset stomach
Thiazolidinediones, also known as glitazones or TZDs, are compounds that lower the body’s insulin intolerance (muscle and fat tissues)
Rosiglitazone: Avandia®	Tablets of 2 mg (pink), 4 mg (orange), and 8 mg (red-brown)	Initially: 4 mg per day. Range: 4-8 mg. Take it once or twice every day	May 1999	SE: Bone loss and fractures in women, anemia, edema from fluid retention, weight increase, macular edema (in the eye), and may raise the chance of heart issues, such as angina or heart attacks, which are caused by the heart (myocardial infarction) may lead to or exacerbate cardiac failure. You cannot use this without severe heart failure or liver disease. Liver surveillance is necessary
Pioglitazone (preferred over rosiglitazone): Actos®	Tablets, 15 mg, 30 mg, and 45 mg (white to off-white)	15-30 mg initially; 15-45 mg daily. Dose: One dose per day	July 1999	SE: Bone loss and fractures in women, anemia, edema from fluid retention, weight increase, macular edema (in the eye), and may lead to or exacerbate cardiac failure. You cannot use this without severe heart failure or liver disease. Liver surveillance is necessary
GLP-1 analogs: Make more insulin, stop the liver from releasing glucose after meals, keep the stomach from emptying as quickly, and make people feel full
Dulaglutide: Trulicity®	1.5 mg or 0.75 mg each time. Under the epidermis (subcutaneous/SQ), injected available in single-dose, dose-specific pen instruments	At first: 0.75 mg once per week. Range: If the reaction is insufficient, it may be increased to 1.5 mg once weekly	September 2014	SE: Sickness, diarrhea, throwing up, stomach pain. It can’t be used if you have multiple endocrine neoplasia syndrome type 2 or if you have a family history of medullary thyroid cancer (MEN2). In patients with a history of medullary thyroid cancer, it is contraindicated; there have been a few cases of pancreatitis (inflammation of the pancreas)
Albiglutide: Tanzeum®	30 mg or 50 mg each time under the epidermis (subcutaneous/SQ), injected calls for rebuilding available in single-dose pens with a particular dose	Initial: 30 mg once weekly. Range: Can increase to 50 mg once weekly if inadequate response	September 2014	SE: Upper respiratory infection, nausea, and injection site response. Infrequent cases of pancreatitis (inflammation of the pancreas); contraindicated in patients with a history of medullary thyroid cancer
SGLT2 inhibitors: Make people pee out more glucose
Dapagliflozin: Farxiga®	5 mg tablets are yellow and round, and 10 mg tablets are yellow and diamond-shaped	5 mg once every day at first. Up to 10 mg per day	January 2014	SE: Increased urination, UT infections, genital yeast infections, dizziness, lower blood pressure, increase in blood potassium; rare severe allergic reactions (severe rash; swelling of the pharynx tongue, body or face) (swelling of the tongue, throat, face or body; severe inflammation). If you have kidney difficulties, you cannot use this product
Empagliflozin: Jardiance®	Tablets 10 mg (pale, beige, round) and 25 mg (pale, beige rectangular)	Initial: 10 mg once daily. Range: Up to 25 mg daily	August 2014	SE: Rare severe allergic responses; side effects including frequent urination, low blood pressure, dizziness, genital yeast infections, and urinary tract infections; and a rise in blood potassium (swelling of tongue, throat, face, or body; severe rash). Do not take it if you have renal disease
Canagliflozin: Invokana®	Tablets come in two different dosages and pill colors: 100 mg (colored yellow) and 300 mg (colored white)	At first: 100 mg every day. Range: 100-300 mg per day. Dose: One dose per day	March 2013	SE: Side effects include frequent or urgent urination, low blood pressure, dizziness, genital yeast infections, UTIs, a rise in blood potassium, and severe but uncommon allergic reactions (swelling of the tongue, throat, face, or body, severe rash). Do not take it if you have renal disease
DPP-4 inhibitors: Increased insulin production and decreased post-meal liver glucose release are two effects
Linagliptin: Tradjenta®	5 mg (red-light) tablet	At first, 5 mg every day. Dose: One dose per day	May 2011	SE: No weight gain, nasal congestion, throat pain, rare reports of pancreatitis, extremely rare severe allergic reactions
Saxagliptin: Onglyza®	2.5 mg tablets are pale to light yellow, and 5 mg tablets are pink	Range: 2.5-5 mg daily, starting with 2.5 or 5 mg. Dose: One dose per day	July 2009	SE: Headache, urinary tract illness, and upper respiratory infection. No gaining weight: If kidney issues exist, lower amounts are used
Sitagliptin: Januvia®	Tablets of 25 mg (pink), 50 mg (light brown), and 100 mg (beige)	At first, take 100 mg every day. Daily dose: 25-100 mg. Dosage: Once every day	December 2006	SE: Symptoms include a runny nose, upper respiratory infection, and uncommon severe allergic responses (swelling of the tongue, throat, face, or body, severe rash). There has been no weight increase. If there are kidney issues, lower doses are used
Alogliptin: Nesina®	Tablets of 6.25 mg (light pink), 12.5 mg (yellow), and 25 mg (light red)	Every day, take 25 mg by mouth. Given once a day	January 2013	SE: Upper respiratory infection, headache, sore throat, stuffy or runny nose, uncommon serious allergic responses (swelling of the tongue, throat, face, or body), and severe rash. Accounts of pancreatitis are uncommon. No weight increase
α-glucosidase inhibitors: STARCH blockers are substances that slow down the digestive process and the assimilation of carbohydrates
Acarbose: Precose® various generics	Tablets of 25 mg, 50 mg, and 100 mg	Initial: Three times per day, 25 mg, 75 to 300 mg. Maximum 150 mg if under 60 kg. Dose: Three times per day	September 1995	SE: Defecation. Take with the first mouthful of your meal. To avoid GI intolerance, begin with a modest dose and gradually increase it
Stimulators of insulin release (insulin secretagogues): Raise the amount of insulin the liver produces
Glinides
Nateglinide: Starlix®	Tablets of 60 mg (pink) and 120 mg (yellow)	120 mg three times every day at first (if A1C is close to goal, use 60 mg). Range: 180-360 mg daily dosage is three times	December 2000	SE: Syndrome of uncontrolled hypoglycemia protection for the aged. Only 2 h of actual playtime are involved. Take it within 30 min of dinner
Repaglinide: Prandin®	Tablets of 0.5 mg (white), 1 mg (yellow), and 2 mg (red)	Starting dose: 1-2 mg daily (0.5 mg if A1C 8%). From 0.5 to 16 mg. The maximum dose is 4 mg per dinner. Given twice, three times, or four times per day	December 1997	SE: Hypoglycemic. It is safe for older adults. The activity lasts only 4 h. Take 15-30 min after eating
SFUs
Glimepiride: Amaryl® various generics	Tablets ranging from 1 mg to 4 mg	To start, try 1-2 mg once a day. Between 1 and 8 mg. One daily dose is recommended	November 1995	SE: Weight increase and hypoglycemia. Only one daily dose is necessary
Glyburide, micronized: Glynase PresTab® various generics	Tablets with dosages of 1.5 mg, 3 mg, 4.5 mg, and 6 mg	Initial: 1.5-3 mg/d; permitted range: 0.75-12 mg. Dosage: One or two daily doses (if > 6 mg)	March 1992	SE: Weight increase and hypoglycemia
Glyburide: Micronase®, DiaBeta® various generics	Tablets of 1.25 mg, 2.5 mg, and 5 mg	Initial: 2.5-5 mg everyday. Range: 1.25-20 mg. To be consumed once or twice every day	May 1984	SE: Hypoglycemia and obesity are possible side effects
Glipizide: Glucotrol®, Glucotrol XL® various generics	Tablets of 5 mg and 10 mg. Tablets of 2.5 mg, 5 mg, and 10 mg ER	At first, 5 mg every day. From 2.5 to 40 mg (20 mg for XL). Dosage: once or twice daily (if more than 15 mg)	May 1984. April 1994	SE: Hypoglycemia and weight increase are symptoms of SE. SFU is preferred by the aged. ER means extended-release/once-daily
Oral pills in combination
Empagliflozin/metformin, Synjardy®	12.5 mg/500 mg (pale brownish purple), 12.5 mg/1000 mg (dark brownish purple), 5 mg/500 mg (orange-yellow), 5 mg/1000 mg (brownish yellow). Tablet with an oval sheet coating	Starting dose: 5 mg/500 mg or 5 mg/1000 mg. Maximum dose: 25 mg/2000 mg split into two doses	January 2015	SE: It’s the same deal with empagliflozin and metformin
Empagliflozin/linagliptin, Glyxambi®	Triangular pills, 10 mg/5 mg (pale yellow), 25 mg/5 mg (pale pink)	At first: 10 mg/5 mg once every day. Range: 5 mg once every day up to 25 mg	February 2015	SE: All the same applies to empagliflozin and linagliptin
Dapagliflozin/metformin XR, Xigduo XR®	10 mg/500 mg (pink), 10 mg/1000 mg (pink to dark pink), and 5 mg/500 mg (orange) (yellow to dark yellow) oval tablets covered in celluloid	Starting dose: The patient’s present regimen up to 10 mg/2000 mg per day	October 2014	SE: Dapagliflozin and metformin are the same as previously mentioned
Canagliflozin/metformin, Invokamet®	Film-coated capsule-shaped pills, 50 mg/500 mg (white), 50 mg/1000 mg (beige), 150 mg/500 mg (yellow), and 150 mg/1000 mg (purple)	Beginning: With 50 mg/500 mg or 50 mg/1000 mg. Range: 300 mg to 2000 mg. Taken in 2 divided quantities	August 2014	SE: Identical to the preceding, but with metformin and canagliflozin
Alogliptin/pioglitazone, Oseni®	The next round of pills is available: 25 mg/45 mg (red), 25 mg/30 mg (peach), 25 mg/15 mg (yellow), 12.5 mg/15 mg (pale yellow), 12.5 mg/30 mg (pale peach), 12.5 mg/45 mg (pale red)	Initial dosage: Once daily, 12.5/15 mg. Range: 25/45 mg and higher ingested with or without food once daily	January 2013	SE: The same applies to pioglitazone and alogliptin
Alogliptin/metformin, Kazano®	Oblong pills, 12.5 mg/1000 mg (pale yellow), 12.5 mg/500 mg (pale yellow)	At first: 12.5 mg/500 mg once or twice every day. Maximum range: 25/2000 taken with meals twice a day	January 2013	SE: Alogliptin and metformin in the same way as previously
Linagliptin/metformin, Jentadueto®	Oval pills with dosages of 2.5 mg/1000 mg (light pink), 2.5 mg/850 mg (light orange), and 2.5 mg/500 mg (golden yellow)	Initial dosage: 2 times a day with food, 2.5 mg/500 mg. Range: Twice daily dosages of up to 2.5 mg/1000 mg food	January 2012	SE: With linagliptin and metformin, the same as above
Sitagliptin/metformin, Janumet XR®	Oval pills, 50 mg/500 mg (light blue), 50 mg/1000 mg (light green), and 100 mg/1000 mg (blue)	At first: 100 mg/1000 mg every day. Maximum daily dose: 100 mg/2000 mg. Dosage: Once every day	February 2012	SE: As with sitagliptin and metformin, the same rules apply
Saxagliptin/metformin XR, Kombiglyze XR®	Capsule-shaped pills contain 2.5 mg/1000 mg (pale yellow to light yellow), 5 mg/1000 mg (pink), and 5 mg/500 mg (golden brown to brown)	Starting dose: 5 mg/500 mg or 5 mg/1000 mg once daily. Maximum dose: 5 milligrammes/2000 mg. Dosage: Once every day	November 2010	SE: The same holds for metformin and saxagliptin

SE: Represent potential side effects of the drug. SFUs: Sulfonylureas; TZD: Thiazolidinediones; GLP: Glucagon-like peptide; DDP: Dipeptidyl peptidase; UTI: Urinary tract infection; ER: Extended release; FDA: Food and Drug Administration.

Table 2 A list of recently developed novel anti-diabetic targets and their method of activities

Nature	Special targets	Diabetics	Method of activity	Ref.
Gene	Gene therapy	Auto-reactive T cells need to be stopped from killing islet cells	Act by fixing or modifying the problematic genes	[81]
Glycoprotein in serum	SERPIN A12 or vaspin	KLK7 reduction enhances insulin signaling and lengthens the half-life of insulin, contributing to lower blood sugar levels	Vaspin blocks KLK7	[89]
Adipokine	Metrnl	Enhanced insulin responsiveness	Cause of PPAR pathway upregulation	[92]
Hormone	ACRP-30	Acrp30 increases insulin sensitivity and lowers blood sugar	Low amounts bring on insulin sensitivity	[106]
Glucocorticoids	11β-HSD1	11β-HSD inhibition glucose reduction, insulin sensitivity improvement	Increasing amounts lead to glucose sensitivity	[85]
Glycoprotein	Fetuin-A	When fetuin-A levels are low, insulin sensitivity will go up	Associated with beta-cell inflammation	[86]
Glycoprotein	GPER	Boost insulin production	Through binding with Gi/o and Gs proteins, glucose homeostasis is regulated	[94]
Glycoprotein	PEDF	Insulin sensitivity is improved by reducing PEDF levels	Insulin resistance is caused by an upregulated chain of kinase-mediated Serine/threonine phosphorylation of IRS	[99]
Protein	Visfatin	Activity that mimics insulin	Receptor for insulin that it binds to	[103]
Protein	CCN3/NOV	Improved glucose tolerance and insulin sensitivity	Strong correlation with hs-CRP	[97]
Glycoprotein	PTP1B		Inhibits insulin signaling by dephosphorylating insulin receptor kinase	[83]

KLK7: Kallikrein 7; PPAR: Peroxisome proliferator-activated receptor; 11β-HSD1: 11 beta-hydroxysteroid dehydrogenase 1; GPER: G protein-coupled estrogen receptor; PEDF: Pigment epithelium-derived factor; CCN3/NOV: Cellular communication network 3/nephroblastoma overexpressed; PTP1B: Protein tyrosine phosphatase 1B; hs-CRP: High-sensitivity C-reactive protein.