What the clinical trials found: A phase III study suggested that exenatide LAR may offer improved blood glucose control over the currently marketed formulation, Byetta.

Adis R&D Insights Rating & Comment: 70. Exenatide LAR is expected to replace the existing, immediate-release formulation of exenatide (Byetta), also developed by Amylin and Lilly. Byetta requires twice daily subcutaneous administration, so a once-weekly formulation would be a more convenient option. An NDA for exenatide LAR is expected to be submitted in 2009, and if approved, the agent is predicted to supersede Byetta as an adjunctive therapy in patients with type-2 diabetes mellitus.

What the analysts had to say:

* In the GLP-1 class, interest will remain high, given the need for better post-prandial control, beta cell preservation and weight control. But competitors will have to demonstrate clear and meaningful benefits for acceptance by physicians, payers and patients.

-David Jacobson, SVP, GfK Market Measures

* We believe exenatide LAR has now demonstrated the most convincing clinical profile of all GLP-ls to date. Efficacy appears to be best in class. We forecast $2 billion in peak sales.

-ING Wholesale Banking's Tun Race

Liraglutide Novo Nordisk

Indication: Type-2 diabetes mellitus (Ph.III)

What the clinical trials found: Phase III clinical trials found oncedaily liraglutide + glimepiride gave superior glycemic control compared with a rosiglitazone-glimepiride combination and with glimepiride monotherapy. The triple combination of glimepiride, metformin and liraglutide was also superior to glimepiride, metformin and insulin glargine. Notably, three trials demonstrated that liraglutide promoted weight loss and had a good safety profile with no serious adverse events reported.

Adis R&D Insights Rating & Comment: 72. Liraglutide may face direct competition from exenatide LAR. A direct, head-to-head study of liraglutide vs. exenatide, initiated this year, may show which is the more effective agent in maintaining glycemic control and hence provide a better therapeutic option for patients with type 2 diabetes.

What the analysts had to say:

* Long-term we have reduced our 2013 sales for liraglutide form $1.3 billion to $1.1 billion reflecting the potential for exenatide LAR to dominate the market. If liraglutide reaches the market, Novo Nordisk is likely to have significant competition to its only major new compound.

-ING Wholesale Banking's Tun Race

Saxagliptin Bristol-Myers Squibb/AstraZeneca/Otsuka

Indication: Type-2 diabetes mellitus (Ph.III)

What the clinical trials found: Preliminary six-month data from a phase III study in patients with type 2 diabetes, which was poorly controlled with metformin, showed that add-on, once daily saxagliptin was safe and well tolerated. The compound significantly improved glycemic control compared with metformin alone. Saxagliptin is currently in phase III multi-center clinical trials worldwide. BMS and AZ plan to file an NDA with the FDA in the first-half of 2008. Studies are assessing the compounds as monotherapy, as an adjunct to diet and exercise, and as an add-on therapy in combination with metformin, sulfonylurea or thaizolizinediones.

Adis R&D Insights Rating & Comment: 74. It remains to be seen whether saxagliptin will have a successful run in the diabetes market. Its future depends on the results from pending clinical trials and its ability to outperform other gliptins already on the market.

What the analysts had to say:

* Saxagliptin is emerging as a serious competitor to Merck's Januvia.

-Rodman & Renshaw 's Michael King

* Saxagliptin could add $750 million to peak US sales by 2017.

-Lehman Brothers PharmaPipelines estimates,

cited by Adis R&D Insight

OTHER KEY PRODUCTS IN THE DIABETES PIPELINE

AJD 101 Ajinomoto/Sankyo

Diabetes (Ph.I)

Insulin inhalation Alkermes/Eli Lilly

Diabetes (Ph.III)

DiaPep277 Andromeda

Type 1 diabetes (Ph.III), Latent autoimmune diabetes in adults (Ph.II)

AZD AstraZeneca

Diabetes (Ph.I)

AZD 2207 AstraZeneca

Diabetes (Ph.I)

BAY 737977 Bayer

Diabetes (Ph.I)

Insulin inhalation Baxter

Diabetes (Ph.I)

Insulin inhalation Coremed

Diabetes (Ph.I)

Insulin oral Coremed

Diabetes (Ph.I)

Diabetes mellitus vaccine Diamyd Medical

Latent autoimmune diabetes in adults (Ph. I), Type 1 diabetes (Ph.II)

LABI Flamel/BristoWAyers Squibb

Diabetes (Ph.II)

Metformin XL Flamel

Diabetes (Ph.II)

KRP 101 Kyorin

Diabetes (Ph.II)

MK 0533 Merck

Diabetes (Ph.II)

MK 0893 Merck

Diabetes (Ph.I)

MK 0941 Merck

Diabetes (Ph.I)

MK 3887 Merck

Diabetes (Ph.I)

MP 513 Mitsubishi/Mitsubishi Tanabe

Diabetes (Ph.II)

Aliskiren Novartis Hypertension in diabetes (Ph.III),

Diabetic nephropathies (Ph.II)

Insulin inhalation QDose

Diabetes (Ph.I)